Systems, devices, and methods for focal ablation

ABSTRACT

Systems, devices, and methods for electroporation ablation therapy are disclosed, with the device including a set of splines coupled to a catheter for medical ablation therapy. Each spline of the set of splines may include a set of electrodes formed on that spline. The set of splines may be configured for translation to transition between a first configuration and a second configuration.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/874,721, filed on Jan. 18, 2018, which claims priority to U.S.Provisional Application No. 62/529,268, filed on Jul. 6, 2017, thedisclosure of each of which is hereby incorporated by reference in itsentirety.

BACKGROUND

The generation of pulsed electric fields for tissue therapeutics hasmoved from the laboratory to clinical applications over the past twodecades, while the effects of brief pulses of high voltages and largeelectric fields on tissue have been investigated for the past fortyyears or more. Application of brief high DC voltages to tissue maygenerate locally high electric fields typically in the range of hundredsof volts per centimeter that disrupt cell membranes by generating poresin the cell membrane. While the precise mechanism of thiselectrically-driven pore generation or electroporation continues to bestudied, it is thought that the application of relatively brief andlarge electric fields generates instabilities in the lipid bilayers incell membranes, causing the occurrence of a distribution of local gapsor pores in the cell membrane. This electroporation may be irreversibleif the applied electric field at the membrane is larger than a thresholdvalue such that the pores do not close and remain open, therebypermitting exchange of biomolecular material across the membrane leadingto necrosis and/or apoptosis (cell death). Subsequently, the surroundingtissue may heal naturally.

While pulsed DC voltages may drive electroporation under the rightcircumstances, there remains an unmet need for thin, flexible,atraumatic devices that effectively deliver high DC voltageelectroporation ablation therapy selectively to endocardial tissue inregions of interest while minimizing damage to healthy tissue.

SUMMARY

Described here are systems, devices, and methods for ablating tissuethrough irreversible electroporation. Generally, a device for deliveringa pulse waveform to tissue may include an ablation device including aset of splines coupled to a catheter. Each spline of the set of splinesmay include a set of electrodes formed on that spline. The set ofsplines may be configured to transition between a first configurationand a second configuration. The ablation device may be configured fordelivering the pulse waveform to tissue during use via one or morespline of the set of splines. As used herein, the terms “spline” and“spine” may be used interchangeably. In some embodiments, an apparatusmay include a catheter defining a longitudinal axis, and a set ofsplines coupled to the catheter, with each spline of the set of splinesincluding a set of electrodes formed on that spline. Each set ofelectrodes may include a distal electrode having an exposed portion suchthat the set of splines includes a set of distal electrodes. A capelectrode may be formed on a distal end of the catheter, with eachdistal electrode being the nearest to the cap electrode relative toother electrodes of its corresponding set of electrodes on the samespline. The cap electrode and each distal electrode of the set of distalelectrodes may have the same electrical polarity during use. The set ofsplines may be configured for translation along the longitudinal axis totransition between a first configuration where the set of splines areapproximately parallel to the longitudinal axis, and a secondconfiguration where a distal portion of each spline of the set ofsplines bows radially outward from the longitudinal axis. The capelectrode may be separated from each distal electrode of the set ofdistal electrodes by at most about 3 mm.

In some embodiments, the exposed portion of each distal electrode of theset of distal electrodes may be exposed along a portion of thecircumference of its corresponding spline. The exposed portion of eachof the distal electrodes may face away from the longitudinal axis in thefirst configuration. The exposed portion of each distal electrode of theset of distal electrodes may subtend an angle of between about 30degrees to about 300 degrees about a center of its corresponding spline.The set of distal electrodes may have a diameter of between about 0.5 mmand about 3 mm. The cap electrode may have a cross-sectional diameter ofbetween about 1 mm and about 5 mm.

In some embodiments, each set of electrodes may include a set ofproximal electrodes. The distal electrodes and the set of proximalelectrodes for a given spline may have opposite electrical polaritiesfor ablation delivery. The cap electrode and the set of distalelectrodes may be collectively configured as an anode. Each distalelectrode of the set of distal electrodes may have a length betweenabout 0.5 mm and about 5 mm. The set of splines when deployed in thesecond configuration may form a shape with an effective cross-sectionaldiameter at its largest portion of between about 6 mm to about 24 mm.

In some embodiments, an outer shaft may define a lumen therethrough. Theset of splines may extend from a distal end of the lumen between about 6mm and about 30 mm. The insulated electrical leads may be configured forsustaining a voltage potential of at least about 700 V withoutdielectric breakdown of its corresponding insulation. The cap electrodemay be independently addressable. The cap electrode and each electrodeof the set of electrodes may be independently addressable. Eachelectrode of the set of electrodes may have an insulated electrical leadassociated therewith. The insulated electrical leads may be disposed ina body of each of the one or more splines.

In some embodiments, an apparatus may include a catheter defining alongitudinal axis, and a set of splines coupled to the catheter. Eachspline of the set of splines may include a set of electrodes formed onthat spline. Each set of electrodes may include a distal electrodehaving an exposed portion such that the set of splines includes a set ofdistal electrodes. The exposed portion of each distal electrode of theset of distal electrodes may subtend an angle relative to its spline ofbetween about 30 degrees and about 300 degrees about a center of itscorresponding spline. A cap electrode may be formed on a distal end ofthe catheter. The set of splines may be configured for translation alongthe longitudinal axis to transition between a first configuration wherethe set of splines are generally parallel to the longitudinal axis and asecond configuration where a distal portion of each spline of the set ofsplines bows radially outward from the longitudinal axis.

In some embodiments, the cap electrode may be separated from each distalelectrode of the set of distal electrodes by at most about 3 mm. Eachdistal electrode of the set of distal electrodes may partially encirclethe circumference of its corresponding spline. The exposed portions ofeach of the set of distal electrodes may face away from the longitudinalaxis in the first configuration. The set of distal electrodes may have adiameter of between about 0.5 mm and about 3 mm. The cap electrode mayhave a cross-sectional diameter of between about 1 mm and about 5 mm.Each set of electrodes may include a set of proximal electrodes, withthe distal electrode and the set of proximal electrodes for a givenspline having opposite electrical polarities during ablation energydelivery. The cap electrode and the set of distal electrodes may becollectively configured as an anode. Each distal electrode of the set ofdistal electrodes may have a length between about 0.5 mm and about 5.0mm. The set of splines when deployed in the second configuration mayform a shape with an effective cross-sectional diameter at its largestsection of between about 6 mm and about 24 mm.

In some embodiments, an outer shaft may define a lumen therethrough,where the set of splines extends from a distal end of the lumen betweenabout 6 mm and about 24 mm. The insulated electrical leads may beconfigured for sustaining a voltage potential of at least about 700 Vwithout dielectric breakdown of its corresponding insulation. The capelectrode may be independently addressable. The cap electrode and eachelectrode of the set of electrodes may be independently addressable.Each electrode of the set of electrodes may have an insulated electricallead associated therewith. The insulated electrical leads may bedisposed in a body of each of the one or more splines.

In some embodiments, an apparatus may include a catheter shaft defininga longitudinal axis, and a set of splines coupled to the catheter shaft.Each spline of the set of splines may include a set of electrodes formedon that spline. Each set of electrodes may include a distal electrodesuch that the set of splines includes a set of distal electrodes. A capelectrode may be formed on a distal end of the catheter. The set ofsplines may be configured for translation along the longitudinal axis totransition between a first configuration where the set of splines aregenerally parallel to the longitudinal axis and a second configurationwhere a distal portion of each spline of the set of splines bowsradially outward from the longitudinal axis. The cap electrode may beseparated from each distal electrode of the set of distal electrodes byat most about 3 mm and the distal portion of each spline of the set ofsplines may be angled between about 60 degrees and about 90 degreesrelative to the longitudinal axis.

In some embodiments, each distal electrode of the set of distalelectrodes may have an exposed portion that subtends an angle of betweenabout 30 degrees and about 300 degrees about a center of itscorresponding spline.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of an electroporation system, according toembodiments.

FIG. 2 is a perspective view of an ablation catheter, according toembodiments.

FIG. 3 is a perspective view of an ablation catheter, according to otherembodiments.

FIG. 4 is a perspective view of an ablation catheter, according to otherembodiments.

FIG. 5 is a detailed perspective view of a distal portion of an ablationcatheter, according to other embodiments.

FIG. 6 is a side view of an ablation catheter, according to otherembodiments.

FIG. 7 is a side view of an ablation catheter, according to otherembodiments.

FIGS. 8A-8B are views of an ablation catheter, according to otherembodiments. FIG. 8A is a side view and FIG. 8B is a frontcross-sectional view.

FIG. 9A is a side view of an ablation catheter in a first structure,according to other embodiments. FIG. 9B is a side view of an ablationcatheter in a second expanded structure, according to other embodiments.FIG. 9C is a side view of an ablation catheter in a third expandedstructure, according to other embodiments. FIG. 9D is a side view of anablation catheter in a fourth expanded structure, according to otherembodiments. FIG. 9E is a side view of an ablation catheter in a fifthexpanded structure, according to other embodiments.

FIG. 10 is a perspective view of a balloon ablation catheter disposed ina left atrial chamber of a heart, according to other embodiments.

FIG. 11 is a cross-sectional view of a balloon ablation catheterdisposed in a left atrial chamber of a heart, according to otherembodiments.

FIGS. 12A-12B are schematic views of a return electrode of an ablationsystem, according to embodiments. FIG. 12A illustrates an unenergizedelectrode and FIG. 12B illustrates an energized electrode.

FIG. 13 illustrates a method for tissue ablation, according toembodiments.

FIG. 14 illustrates a method for tissue ablation, according to otherembodiments.

FIG. 15 is an illustration of the ablation catheter depicted in FIG. 2disposed in a left atrial chamber of a heart.

FIG. 16 is an illustration of the ablation catheter depicted in FIG. 3disposed in a left atrial chamber of a heart.

FIG. 17 is an illustration of two of the ablation catheters depicted inFIG. 4 disposed in a left atrial chamber of a heart.

FIG. 18 is an illustration of the ablation catheter depicted in FIG. 5disposed in a left atrial chamber of a heart.

FIGS. 19A-19B are illustrative views of a set of electrodes disposed ina pulmonary vein ostium, according to other embodiments. FIG. 19A is aschematic perspective view and FIG. 19B is a cross-sectional view.

FIGS. 20A-20B are illustrative views of an electric field generated byelectrodes disposed in a pulmonary vein ostium, according to otherembodiments. FIG. 20A is a schematic perspective view and FIG. 20B is across-sectional view.

FIG. 21 is an example waveform showing a sequence of voltage pulses witha pulse width defined for each pulse, according to embodiments.

FIG. 22 schematically illustrates a hierarchy of pulses showing pulsewidths, intervals between pulses, and groupings of pulses, according toembodiments.

FIG. 23 provides a schematic illustration of a nested hierarchy ofmonophasic pulses displaying different levels of nested hierarchy,according to embodiments.

FIG. 24 is a schematic illustration of a nested hierarchy of biphasicpulses displaying different levels of nested hierarchy, according toembodiments.

FIG. 25 illustrates schematically a time sequence of electrocardiogramsand cardiac pacing signals together with atrial and ventricularrefractory time periods and indicating a time window for irreversibleelectroporation ablation, according to embodiments.

FIG. 26A is a perspective view of an ablation catheter, according toother embodiments. FIG. 26B is a side view of the ablation catheterdepicted in FIG. 26A disposed in a left atrial chamber of a heart,adjacent to a pulmonary ostium. FIG. 26C is a top view of a simulationof the ablation catheter depicted in FIG. 26B, illustrating selectiveelectrode activation according to embodiments. FIG. 26D is a simulatedillustration of tissue ablation in a pulmonary ostium, according toembodiments.

FIGS. 27A-27C are each side views of an ablation catheter, according toother embodiments. FIG. 27A is a side view of the ablation catheter in asecond configuration. FIG. 27B is another side view of the ablationcatheter in the second configuration. FIG. 27C is yet another side viewof the ablation catheter in the second configuration.

FIG. 28 is a side view of an ablation catheter, according to otherembodiments.

FIGS. 29A-29D are cross-sectional side views of an ablation catheter,according to other embodiments. FIG. 29A is a cross-sectional side viewof the ablation catheter in a first configuration. FIG. 29B is across-sectional side view of the ablation catheter in a thirdconfiguration. FIG. 29C is another cross-sectional side view of theablation catheter in the third configuration. FIG. 29D is yet anothercross-sectional side view of the ablation catheter in the thirdconfiguration.

FIG. 30 is a side view of an ablation catheter, according to otherembodiments.

FIGS. 31A-31B are perspective views of an ablation catheter, accordingto other embodiments. FIG. 31A is a perspective view of the ablationcatheter in a first configuration. FIG. 31B is a perspective view of theablation catheter in a second configuration.

FIG. 32 is a cross-sectional schematic view of an ablation catheter,according to other embodiments.

FIGS. 33A-33E are illustrative views of an ablation catheter, accordingto other embodiments. FIG. 33A is a perspective view of the ablationcatheter. FIG. 33B is a front view of the ablation catheter of FIG. 33A.FIG. 33C is a cut-away perspective view of a spline of the ablationcatheter of FIG. 33A. FIG. 33D is a cross-sectional view of a spline ofthe ablation catheter of FIG. 33A. FIG. 33E is a perspective view of theablation catheter of FIG. 33A disposed adjacent to tissue.

DETAILED DESCRIPTION

Described herein are systems, devices, and methods for selective andrapid application of pulsed electric fields to ablate tissue byirreversible electroporation. Generally, the systems, devices, andmethods described herein may be used to generate large electric fieldmagnitudes at desired regions of interest and reduce peak electric fieldvalues elsewhere in order to reduce unnecessary tissue damage andelectrical arcing. An irreversible electroporation system as describedherein may include a signal generator and a processor configured toapply one or more voltage pulse waveforms to a selected set ofelectrodes of an ablation device to deliver energy to a region ofinterest (e.g., ablation energy for a set of tissue in a pulmonary veinostium). The pulse waveforms disclosed herein may aid in therapeutictreatment of a variety of cardiac arrhythmias (e.g., atrialfibrillation). In order to deliver the pulse waveforms generated by thesignal generator, one or more electrodes of the ablation device may havean insulated electrical lead configured for sustaining a voltagepotential of at least about 700 V without dielectric breakdown of itscorresponding insulation. The electrodes may be independentlyaddressable such that each electrode may be controlled (e.g., deliverenergy) independently of any other electrode of the device. In thismanner, the electrodes may deliver different energy waveforms withdifferent timing synergistically for electroporation of tissue.

The term “electroporation” as used herein refers to the application ofan electric field to a cell membrane to change the permeability of thecell membrane to the extracellular environment. The term “reversibleelectroporation” as used herein refers to the application of an electricfield to a cell membrane to temporarily change the permeability of thecell membrane to the extracellular environment. For example, a cellundergoing reversible electroporation can observe the temporary and/orintermittent formation of one or more pores in its cell membrane thatclose up upon removal of the electric field. The term “irreversibleelectroporation” as used herein refers to the application of an electricfield to a cell membrane to permanently change the permeability of thecell membrane to the extracellular environment. For example, a cellundergoing irreversible electroporation can observe the formation of oneor more pores in its cell membrane that persist upon removal of theelectric field.

Pulse waveforms for electroporation energy delivery as disclosed hereinmay enhance the safety, efficiency and effectiveness of energy deliveryto tissue by reducing the electric field threshold associated withirreversible electroporation, thus yielding more effective ablativelesions with a reduction in total energy delivered. In some embodiments,the voltage pulse waveforms disclosed herein may be hierarchical andhave a nested structure. For example, the pulse waveform may includehierarchical groupings of pulses having associated timescales. In someembodiments, the methods, systems, and devices disclosed herein maycomprise one or more of the methods, systems, and devices described inInternational Application Serial No. PCT/US2016/057664, filed on Oct.19, 2016, and titled “SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OFABLATIVE ENERGY TO TISSUE,” the contents of which are herebyincorporated by reference in its entirety.

In some embodiments, the systems may further include a cardiacstimulator used to synchronize the generation of the pulse waveform to apaced heartbeat. The cardiac stimulator may electrically pace the heartwith a cardiac stimulator and ensure pacing capture to establishperiodicity and predictability of the cardiac cycle. A time windowwithin a refractory period of the periodic cardiac cycle may be selectedfor voltage pulse waveform delivery. Thus, voltage pulse waveforms maybe delivered in the refractory period of the cardiac cycle so as toavoid disruption of the sinus rhythm of the heart. In some embodiments,an ablation device may include one or more catheters, guidewires,balloons, and electrodes. The ablation device may transform intodifferent configurations (e.g., compact and expanded) to position thedevice within an endocardial space. In some embodiments, the system mayoptionally include one or more return electrodes.

Generally, to ablate tissue, one or more catheters may be advanced in aminimally invasive fashion through vasculature to a target location. Ina cardiac application, the electrodes through which the voltage pulsewaveform is delivered may be disposed on an epicardial device or on anendocardial device. The methods described here may include introducing adevice into an endocardial space of the left atrium of the heart anddisposing the device in contact with a pulmonary vein ostium. A pulsewaveform may be generated and delivered to one or more electrodes of thedevice to ablate tissue. In some embodiments, the pulse waveform may begenerated in synchronization with a pacing signal of the heart to avoiddisruption of the sinus rhythm of the heart. In some embodiments, theelectrodes may be configured in anode-cathode subsets. The pulsewaveform may include hierarchical waveforms to aid in tissue ablationand reduce damage to healthy tissue.

I. Systems Overview

Disclosed herein are systems and devices configured for tissue ablationvia the selective and rapid application of voltage pulse waveforms toaid tissue ablation, resulting in irreversible electroporation.Generally, a system for ablating tissue described here may include asignal generator and an ablation device having one or more electrodesfor the selective and rapid application of DC voltage to driveelectroporation. As described herein, the systems and devices may bedeployed epicardially and/or endocardially to treat atrial fibrillation.Voltages may be applied to a selected subset of the electrodes, withindependent subset selections for anode and cathode electrodeselections. A pacing signal for cardiac stimulation may be generated andused to generate the pulse waveform by the signal generator insynchronization with the pacing signal.

Generally, the systems and devices described herein include one or morecatheters configured to ablate tissue in a left atrial chamber of aheart. FIG. 1 illustrates an ablation system (100) configured to delivervoltage pulse waveforms. The system (100) may include an apparatus (120)including a signal generator (122), processor (124), memory (126), andcardiac stimulator (128). The apparatus (120) may be coupled to anablation device (110), and optionally to a pacing device (130) and/or anoptional return electrode (140) (e.g., a return pad, illustrated herewith dotted lines).

The signal generator (122) may be configured to generate pulse waveformsfor irreversible electroporation of tissue, such as, for example,pulmonary vein ostia. For example, the signal generator (122) may be avoltage pulse waveform generator and deliver a pulse waveform to theablation device (110). The return electrode (140) may be coupled to apatient (e.g., disposed on a patient's back) to allow current to passfrom the ablation device (110) through the patient and then to thereturn electrode (140) to provide a safe current return path from thepatient (not shown). The processor (124) may incorporate data receivedfrom memory (126), cardiac stimulator (128), and pacing device (130) todetermine the parameters (e.g., amplitude, width, duty cycle, etc.) ofthe pulse waveform to be generated by the signal generator (122). Thememory (126) may further store instructions to cause the signalgenerator (122) to execute modules, processes and/or functionsassociated with the system (100), such as pulse waveform generationand/or cardiac pacing synchronization. For example, the memory (126) maybe configured to store pulse waveform and/or heart pacing data for pulsewaveform generation and/or cardiac pacing, respectively.

In some embodiments, the ablation device (110) may include a catheterconfigured to receive and/or deliver the pulse waveforms described inmore detail below. For example, the ablation device (110) may beintroduced into an endocardial space of the left atrium and positionedto align one or more electrodes (112) to one or more pulmonary veinostia, and then deliver the pulse waveforms to ablate tissue. Theablation device (110) may include one or more electrodes (112), whichmay, in some embodiments, be a set of independently addressableelectrodes. Each electrode may include an insulated electrical leadconfigured to sustain a voltage potential of at least about 700 Vwithout dielectric breakdown of its corresponding insulation. In someembodiments, the insulation on each of the electrical leads may sustainan electrical potential difference of between about 200 V to about 1,500V across its thickness without dielectric breakdown. For example, theelectrodes (112) may be grouped into one or more anode-cathode subsetssuch as, for example, a subset including one anode and one cathode, asubset including two anodes and two cathodes, a subset including twoanodes and one cathode, a subset including one anode and two cathodes, asubset including three anodes and one cathode, a subset including threeanodes and two cathodes, and/or the like.

The pacing device (130) may be suitably coupled to the patient (notshown) and configured to receive a heart pacing signal generated by thecardiac stimulator (128) of the apparatus (120) for cardiac stimulation.An indication of the pacing signal may be transmitted by the cardiacstimulator (128) to the signal generator (122). Based on the pacingsignal, an indication of a voltage pulse waveform may be selected,computed, and/or otherwise identified by the processor (124) andgenerated by the signal generator (122). In some embodiments, the signalgenerator (122) is configured to generate the pulse waveform insynchronization with the indication of the pacing signal (e.g., within acommon refractory window). For example, in some embodiments, the commonrefractory window may start substantially immediately following aventricular pacing signal (or after a very small delay) and last for aduration of approximately 250 ms or less thereafter. In suchembodiments, an entire pulse waveform may be delivered within thisduration.

The processor (124) may be any suitable processing device configured torun and/or execute a set of instructions or code. The processor may be,for example, a general purpose processor, a Field Programmable GateArray (FPGA), an Application Specific Integrated Circuit (ASIC), aDigital Signal Processor (DSP), and/or the like. The processor may beconfigured to run and/or execute application processes and/or othermodules, processes and/or functions associated with the system and/or anetwork associated therewith (not shown). The underlying devicetechnologies may be provided in a variety of component types, e.g.,metal-oxide semiconductor field-effect transistor (MOSFET) technologieslike complementary metal-oxide semiconductor (CMOS), bipolartechnologies like emitter-coupled logic (ECL), polymer technologies(e.g., silicon-conjugated polymer and metal-conjugated polymer-metalstructures), mixed analog and digital, and/or the like.

The memory (126) may include a database (not shown) and may be, forexample, a random access memory (RAM), a memory buffer, a hard drive, anerasable programmable read-only memory (EPROM), an electrically erasableread-only memory (EEPROM), a read-only memory (ROM), Flash memory, etc.The memory (126) may store instructions to cause the processor (124) toexecute modules, processes and/or functions associated with the system(100), such as pulse waveform generation and/or cardiac pacing.

The system (100) may be in communication with other devices (not shown)via, for example, one or more networks, each of which may be any type ofnetwork. A wireless network may refer to any type of digital networkthat is not connected by cables of any kind. However, a wireless networkmay connect to a wireline network in order to interface with theInternet, other carrier voice and data networks, business networks, andpersonal networks. A wireline network is typically carried over coppertwisted pair, coaxial cable or fiber optic cables. There are manydifferent types of wireline networks including, wide area networks(WAN), metropolitan area networks (MAN), local area networks (LAN),campus area networks (CAN), global area networks (GAN), like theInternet, and virtual private networks (VPN). Hereinafter, networkrefers to any combination of combined wireless, wireline, public andprivate data networks that are typically interconnected through theInternet, to provide a unified networking and information accesssolution.

Ablation Device

The systems described here may include one or more multi-electrodeablation devices configured to ablate tissue in a left atrial chamber ofa heart for treating atrial fibrillation. FIG. 2 is a perspective viewof an ablation device (200) (e.g., structurally and/or functionallysimilar to the ablation device (110)) including a catheter (210) and aguidewire (220) slidable within a lumen of the catheter (210). Theguidewire (220) may include a nonlinear distal portion (222) and thecatheter (210) may be configured to be disposed over the guidewire (220)during use. The distal portion (222) of the guidewire (220) may beshaped to aid placement of the catheter (210) in a lumen of the patient.For example, a shape of the distal portion (222) of the guidewire (220)may be configured for placement in a pulmonary vein ostium and/or thevicinity thereof, as described in more detail with respect to FIG. 15.The distal portion (222) of the guidewire (220) may include and/or beformed in an atraumatic shape that reduces trauma to tissue (e.g.,prevents and/or reduces the possibility of tissue puncture). Forexample, the distal portion (222) of the guidewire (220) may include anonlinear shape such as a circle, loop (as illustrated in FIG. 2),ellipsoid, or any other geometric shape. In some embodiments, theguidewire (220) may be configured to be resilient such that theguidewire having a nonlinear shape may conform to a lumen of thecatheter (210) when disposed in the catheter (210), andre-form/otherwise regain the nonlinear shape when advanced out of thecatheter (210). In other embodiments, the catheter (210) may similarlybe configured to be resilient, such as for aiding advancement of thecatheter (210) through a sheath (not shown). The shaped distal portion(222) of the guidewire (220) may be angled relative to the otherportions of the guidewire (220) and catheter (210). The catheter (210)and guidewire (220) may be sized for advancement into an endocardialspace (e.g., left atrium). A diameter of the shaped distal portion (222)of the guidewire (220) may be about the same as a diameter of a lumen inwhich the catheter (230) is to be disposed.

The catheter (210) may be slidably advanced over the guidewire (220) soas to be disposed over the guidewire (220) during use. The distalportion (222) of the guidewire (220) disposed in a lumen (e.g., near apulmonary vein ostium) may serve as a backstop to advancement of adistal portion of the catheter (210). The distal portion of the catheter(210) may include a set of electrodes (212) (e.g., structurally and/orfunctionally similar to the electrode(s) (112)) configured to contact aninner radial surface of a lumen (e.g., pulmonary vein ostium). Forexample, the electrodes (212) may include an approximately circulararrangement of electrodes configured to contact a pulmonary vein ostium.As shown in FIG. 2, one or more electrodes (212) may include a series ofmetallic bands or rings disposed along a catheter shaft and beelectrically connected together. For example, the ablation device (200)may include a single electrode having a plurality of bands, one or moreelectrodes each having its own band, and combinations thereof. In someembodiments, the electrodes (212) may be shaped to conform to the shapeof the distal portion (222) of the guidewire (220). The catheter shaftmay include flexible portions between the electrodes to enhanceflexibility. In other embodiments, one or more electrodes (212) mayinclude a helical winding to enhance flexibility.

Each of the electrodes of the ablation devices discussed herein may beconnected to an insulated electrical lead (not shown) leading to ahandle (not shown) coupled to a proximal portion of the catheter. Theinsulation on each of the electrical leads may sustain an electricalpotential difference of at least 700V across its thickness withoutdielectric breakdown. In other embodiments, the insulation on each ofthe electrical leads may sustain an electrical potential difference ofbetween about 200V to about 2000 V across its thickness withoutdielectric breakdown, including all values and sub-ranges in between.This allows the electrodes to effectively deliver electrical energy andto ablate tissue through irreversible electroporation. The electrodesmay, for example, receive pulse waveforms generated by a signalgenerator (122) as discussed above with respect to FIG. 1. In otherembodiments, a guidewire (220) may be separate from the ablation device(200) (e.g., the ablation device (200) includes the catheter (210) butnot the guidewire (220). For example, a guidewire (220) may be advancedby itself into an endocardial space, and thereafter the catheter (210)may be advanced into the endocardial space over the guidewire (220).

FIG. 3 is a perspective view of another embodiment of an ablation device(300) (e.g., structurally and/or functionally similar to the ablationdevice (110)) including a catheter (310) having a set of electrodes(314) provided along a distal portion (312) of the catheter (310). Thedistal portion (312) of the catheter (310) may be nonlinear and form anapproximately circle shape. A set of electrodes (314) may be disposedalong a nonlinear distal portion (312) of the catheter (310) may form agenerally circular arrangement of electrodes (314). During use, theelectrodes (314) may be disposed at a pulmonary vein ostium in order todeliver a pulse waveform to ablate tissue, as described in more detailwith respect to FIG. 16. The shaped distal portion (312) of the catheter(310) may be angled relative to the other portions of the catheter(310). For example, the distal portion (312) of the catheter (310) maybe generally perpendicular to an adjacent portion of the catheter (310).In some embodiments, a handle (not shown) may be coupled to a proximalportion of the catheter (310) and may include a bending mechanism (e.g.,one or more pull wires (not shown)) configured to modify the shape ofthe distal portion (312) of the catheter (310). For example, operationof a pull wire of the handle may increase or decrease a circumference ofthe circular shape of the distal portion (312) of the catheter (310).The diameter of the distal portion (312) of the catheter (310) may bemodified to allow the electrodes (314) to be disposed near and/or incontact with a pulmonary vein ostium (e.g., in contact with an innerradial surface of the pulmonary vein). The electrodes (314) may includea series of metallic bands or rings and be independently addressable.

In some embodiments, the pulse waveform may be applied between theelectrodes (314) configured in anode and cathode sets. For example,adjacent or approximately diametrically opposed electrode pairs may beactivated together as an anode-cathode set. It should be appreciatedthat any of the pulse waveforms disclosed herein may be progressively orsequentially applied over a sequence of anode-cathode electrodes.

FIG. 4 is a perspective view of yet another embodiment of an ablationdevice (400) (e.g., structurally and/or functionally similar to theablation device (110)) including a catheter (410) and a guidewire (420)having a shaped, nonlinear distal portion (422). The guidewire (420) maybe slidable within a lumen of the catheter (410). The guidewire (420)may be advanced through the lumen of the catheter (410) and a distalportion (422) of the guidewire (420) may be approximately circularshaped. The shape and/or diameter of the distal portion (422) of theguidewire (420) may be modified using a bending mechanism as describedabove with respect to FIG. 3. The catheter (410) may be flexible so asto be deflectable. In some embodiments, the catheter (410) and/orguidewire (420) may be configured to be resilient such that they conformto a lumen in which they are disposed and assume a secondary shape whenadvanced out of the lumen. By modifying a size of the guidewire (420)and manipulating the deflection of the catheter (410), the distalportion (422) of the guidewire (420) may be positioned at a targettissue site, such as, a pulmonary vein ostium. A distal end (412) of thecatheter (410) may be sealed off except where the guidewire (420)extends from such that the catheter (410) may electrically insulate theportion of the guidewire (420) within the lumen of the catheter (410).For example, in some embodiments, the distal end (412) of the catheter(410) may include a seal having an opening that permits passage of theguidewire (420) upon application of force to form a compression hold(that may be fluid-tight) between the seal and the guidewire (420).

In some embodiments, the exposed distal portion (422) of the guidewire(420) may be coupled to an electrode and configured to receive a pulsewaveform from a signal generator and deliver the pulse waveform totissue during use. For example, a proximal end of the guidewire (420)may be coupled to a suitable lead and connected to the signal generator(122) of FIG. 1. The distal portion (422) of the guidewire (420) may besized such that it may be positioned at a pulmonary vein ostium. Forexample, a diameter of the shaped distal portion (422) of the guidewire(420) may be about the same as a diameter of a pulmonary vein ostium.The shaped distal portion (422) of the guidewire (420) may be angledrelative to the other portions of the guidewire (420) and catheter(410).

The guidewire (420) may include stainless steel, nitinol, platinum, orother suitable, biocompatible materials. In some embodiments, the distalportion (422) of the guidewire (420) may include a platinum coilphysically and electrically attached to the guidewire (420). Theplatinum coil may be an electrode configured for delivery of a voltagepulse waveform. Platinum is radiopaque and its use may increaseflexibility to aid advancement and positioning of the ablation device(400) within an endocardial space.

FIG. 5 is a detailed perspective view of a flower-shaped distal portionof an ablation device (500) (e.g., structurally and/or functionallysimilar to the ablation device (110)) including a set of electrodes(520, 522, 524, 526) each extending from a pair of insulated leadsegments (510, 512, 514, 516). Each pair of adjacent insulated leadsegments coupled to an uninsulated electrode (e.g., lead segments (510,512) and electrode (526)) form a loop (FIG. 5 illustrates a set of fourloops). The set of loops at the distal portion of the ablation device(500) may be configured for delivering a pulse waveform to tissue. Theablation device (500) may include a set of insulated lead segments (510,512, 514, 516) that branch out at a distal end of the device (500) toconnect to respective exposed electrodes (520, 522, 524, 526), as shownin FIG. 5. The electrodes (520, 522, 524, 526) may include an exposedportion of an electrical conductor. In some embodiments, one or more ofthe electrodes (520, 522, 524, 526) may include a platinum coil. The oneor more segments (510, 512, 514, 516) may be coupled to a bendingmechanism (e.g., strut, pull wire, etc.) controlled from a handle (notshown) to control a size and/or shape of the distal portion of thedevice (500).

The electrodes (520, 522, 524, 526) may be flexible and form a compactfirst configuration for advancement into an endocardial space, such asadjacent to a pulmonary vein ostium. Once disposed at a desiredlocation, the electrodes (520, 522, 524, 526) may be transformed to anexpanded second configuration when advanced out of a lumen, such as asheath, to form a flower-shaped distal portion, as shown in FIG. 5. Inother embodiments, the insulated lead segments (510, 512, 514, 516) andelectrodes (520, 522, 524, 526) may be biased to expand outward (e.g.,spring open) into the second configuration when advanced out of a lumen(e.g., sheath) carrying the device (500). The electrodes (520, 522, 524,526) may be independently addressable and each have an insulatedelectrical lead configured to sustain a voltage potential of at leastabout 700 V without dielectric breakdown of its correspondinginsulation. In other embodiments, the insulation on each of theelectrical leads may sustain an electrical potential difference ofbetween about 200 V to about 2000 V across its thickness withoutdielectric breakdown.

In some embodiments, the ablation device (5000) may be configured fordelivering the pulse waveform to tissue during use via the set ofelectrodes (520, 522, 524, 526). In some embodiments, the pulse waveformmay be applied between the electrodes (520, 522, 524, 526) configured inanode and cathode sets. For example, approximately diametricallyopposite electrode pairs (e.g., electrodes (520, 524) and (522, 526))may be activated together as an anode-cathode pair. In otherembodiments, adjacent electrodes may be configured as an anode-cathodepair. As an example, a first electrode (520) of the set of electrodesmay be configured as an anode and a second electrode (522) may beconfigured as a cathode.

FIGS. 6-9E, 26A-27C, and 28 illustrate additional embodiments of anablation device (e.g., structurally and/or functionally similar to theablation device (110)) that may be configured to deliver voltage pulsewaveforms using a set of electrodes to ablate tissue and electricallyisolate a pulmonary vein. In some of these embodiments, the ablationdevice may be transformed from a first configuration to a secondconfiguration such that the electrodes of the ablation device expandoutward to contact a lumen of tissue (e.g., pulmonary vein ostium).

FIG. 6 is a side view of an embodiment of an ablation device (600)including a catheter shaft (610) at a proximal end of the device (600),a distal cap (612) of the device (600), and a set of splines (614)coupled thereto. The distal cap (612) may include an atraumatic shape toreduce trauma to tissue. A proximal end of the set of splines (614) maybe coupled to a distal end of the catheter shaft (610), and a distal endof the set of splines (614) may be tethered to the distal cap (612) ofthe device (600). The ablation device (600) may be configured fordelivering a pulse waveform to tissue during use via one or more splinesof the set of splines (614).

Each spline (614) of the ablation device (600) may include one or morejointly wired, or in some cases independently addressable electrodes(616) formed on a surface of the spline (614). Each electrode (616) mayinclude an insulated electrical lead configured to sustain a voltagepotential of at least about 700 V without dielectric breakdown of itscorresponding insulation. In other embodiments, the insulation on eachof the electrical leads may sustain an electrical potential differenceof between about 200V to about 2000 V across its thickness withoutdielectric breakdown. Each spline (614) may include the insulatedelectrical leads of each electrode (616) formed in a body of the spline(614) (e.g., within a lumen of the spline (614)). In cases where theelectrodes on a single spline are wired together, a single insulatedlead may carry strands connecting to different electrodes on the spline.FIG. 6 illustrates a set of splines (614) where each spline (614)includes a pair of electrodes (616) having about the same size, shape,and spacing as the electrodes (616) of an adjacent spline (614). Inother embodiments, the size, shape, and spacing of the electrodes (616)may differ.

For each of the ablation devices described herein, and the ablationdevices described in FIGS. 6-9E, 26A-27C, and 28 in particular, eachspline of the set of splines may include a flexible curvature. Theminimum radius of curvature of a spline can be in the range of about 1cm or larger. For example, the set of splines may form a deliveryassembly at a distal portion of the ablation device and be configured totransform between a first configuration where the set of splines bowradially outward from a longitudinal axis of the ablation device, and asecond configuration where the set of splines are arranged generallyparallel to the longitudinal axis of the ablation device. In thismanner, the splines may more easily conform to the geometry of anendocardial space. In general, the “basket” of splines can have anasymmetric shape along the shaft length, so that one end (say the distalend) of the basket is more bulbous than the other end (say the proximalend) of the basket. The delivery assembly may be disposed in the firstconfiguration in contact with the pulmonary vein ostium and transformedto the second configuration prior to delivering a pulse waveform. Insome of these embodiments, a handle may be coupled to the set of splinesand the handle configured for affecting transformation of the set ofsplines between the first configuration and the second configuration. Insome embodiments, the electrical leads of at least two electrodes of theset of electrodes may be electrically coupled at or near a proximalportion of the ablation device, such as, for example, within the handle.

In one embodiment, each of the electrodes (616) on a spline (614) may beconfigured as an anode while each of the electrodes (616) on an adjacentspline (614) may be configured as a cathode. In another embodiment, theelectrodes (616) on one spline may alternate between an anode andcathode with the electrodes of an adjacent spline having a reverseconfiguration (e.g., cathode and anode). The ablation device (600) mayinclude any number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12,14, 16, 18, 20, or more splines, including all values and sub-ranges inbetween. In some embodiments, the ablation device (600) may include 3 to20 splines. For example, the ablation device (600) may include 6 to 12splines.

FIG. 7 is a side view of another embodiment of an ablation device (700)including a catheter shaft (710) at a proximal end of the device (700),a distal cap (712) of the device (700), and a set of splines (714)coupled thereto. The distal cap (712) may include an atraumatic shape. Aproximal end of the set of splines (714) may be coupled to a distal endof the catheter shaft (710), and a distal end of the set of splines(714) may be tethered to the distal cap (712) of the device (700). Eachspline (714) of the ablation device (700) may include one or moreindependently addressable electrodes (716) formed on a surface of thespline (714). Each electrode (716) may include an insulated electricallead configured to sustain a voltage potential of at least about 700 Vwithout dielectric breakdown of its corresponding insulation. In otherembodiments, the insulation on each of the electrical leads may sustainan electrical potential difference of between about 200V to about 1500 Vacross its thickness without dielectric breakdown. Each spline (714) mayinclude the insulated electrical leads of each electrode (716) formed ina body of the spline (714) (e.g., within a lumen of the spline (714)). Aset of spline wires (718, 719) may be electrically conductive andelectrically couple adjacent electrodes (716) disposed on differentsplines (714) such as electrodes (716) between a pair of splines (718,719) of the set of splines. For example, the spline wires (718, 719) mayextend in a transverse direction relative to a longitudinal axis of theablation device (700).

FIG. 7 illustrates a set of splines (714) where each spline (714)includes a pair of electrodes (716) having about the same size, shape,and spacing as the electrodes (716) of an adjacent spline (714). Inother embodiments, the size, shape, and spacing of the electrodes (716)may differ. For example, the electrodes (716) electrically coupled to afirst spline wire (718) may differ in size and/or shape from electrodes(716′) electrically coupled to a second spline wire (719).

In some embodiments, the first spline wire (718) may include a first setof spline wires (720, 721, 722, 723), where each spline wire of the setof spline wires (720, 721, 722, 723) may couple electrodes (716) betweena different pair of splines of the set of splines (714). In some ofthese embodiments, the set of spline wires (720, 721, 722, 723) may forma continuous loop between the electrodes (716) coupled thereto.Likewise, the second spline wire (719) may include a second set ofspline wires (724, 725, 726), where each spline wire of the set ofspline wires (724, 725, 726) may couple electrodes (716′) across the setof splines (714). The second set of spline wires (724, 725, 726) maycouple different electrodes (716′) across the set of splines (714) thanthe first set of spline wires (720, 721, 722, 723). In some of theseembodiments, the first set of spline wires (720, 721, 722, 723) may forma first continuous loop between the electrodes (716) coupled thereto andthe second set of spline wires (724, 725, 726) may form a secondcontinuous loop between the electrodes (716′) coupled thereto. The firstcontinuous loop may be electrically isolated from the second continuousloop. In some of these embodiments, the electrodes (716) coupled to thefirst continuous loop may be configured as anodes and the electrodes(716) coupled to the second continuous loop may be configured ascathodes. A pulse waveform may be delivered to the electrodes (716) ofthe first and second continuous loop. In some embodiments, the splinewires such as 721, 722, 723 etc. can be replaced by similar electricalconnections in the proximal part of the device (for example, in thedevice handle). For example, the electrodes 716 can all be electricallywired together in the handle of the device.

In another embodiment, the first spline wire (721) of the set of splinewires (720, 721, 722, 723) may couple electrodes (716) between a firstspline (711) and a second spline (713) of the set of splines (714), anda second spline wire (720) of the set of spline wires (720, 721, 722,723) may couple electrodes (716) between the first spline (711) and athird spline (715) of the set of splines (714). The electrodes (716)coupled by the first spline wire (721) and the second spline wire (720)may be configured as an anode and cathode (or vice-versa). In yetanother embodiment, the first spline wire (721) of the set of splinewires (720, 721, 722, 723) may couple the electrodes (716) between afirst spline (711) and a second spline (713) of the set of splines(714), and a second spline wire (723) of the set of spline wires (720,721, 722, 723) may couple the electrodes (716) between a third spline(715) and a fourth spline (717) of the set of splines (714). A pulsewaveform may be delivered to the electrodes (716) coupled by the firstspline wire (721) and the second spline wire (723). In some embodiments,instead of spline wires the electrical leads of at least two electrodesof the set of electrodes are electrically coupled at or near a proximalportion of the ablation device, such as, for example, within a handle.

In other embodiments, one or more of the spline wires (718, 719) mayform a continuous loop between the electrically coupled electrodes(716). For example, a first set of spline wires (718) may form a firstcontinuous loop between the electrodes (716) coupled thereto and asecond set of spline wires (719) may form a second continuous loopbetween the electrodes (716) coupled thereto. In this case, the firstcontinuous loop may be electrically isolated from the second continuousloop. In one embodiment, each of the electrodes (716) coupled to a firstset of spline wires (718) may be configured as an anode while each ofthe electrodes (716) coupled to a second set of spline wires (719) maybe configured as a cathode. Each group of electrically coupledelectrodes (716) may be independently addressable. In some embodiments,instead of spline wires the electrical leads of at least two electrodesof the set of electrodes are electrically coupled at or near a proximalportion of the ablation device, such as, for example, within a handle.

In some embodiments, as discussed in further detail below with respectto FIGS. 8A-8B, a spline wire may electrically couple to a set ofelectrodes (e.g., 2, 3, 4, 5, etc.) without forming a continuous loop.For example, a discontinuous loop may be formed using two spline wires.In other embodiments, the size, shape, and spacing of the electrodes(716) may differ. The ablation device (700) may include any number ofsplines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, ormore splines. In some embodiments, the ablation device (700) may include3 to 20 splines. For example, in one embodiment, the ablation device(700) may include 6 to 9 splines.

FIGS. 8A-8B are side and front cross-sectional views, respectively, ofan ablation catheter (800). FIG. 8A is a side view of an embodiment ofan ablation device (800) including a catheter shaft (810) at a proximalend of the device (800), a distal cap (812) of the device (800), and aset of splines (814) coupled thereto. The distal cap (812) may includean atraumatic shape. A proximal end of the set of splines (814) may becoupled to a distal end of the catheter shaft (810), and a distal end ofthe set of splines (14) may be tethered to the distal cap (812) of thedevice (800). Each spline (814) of the ablation device (800) may includeone or more independently addressable electrodes (816, 818) formed on asurface of the spline (814). Each electrode (816, 818) may include aninsulated electrical lead configured to sustain a voltage potential ofat least about 700 V without dielectric breakdown of its correspondinginsulation. In other embodiments, the insulation on each of theelectrical leads may sustain an electrical potential difference ofbetween about 200V to about 2000 V across its thickness withoutdielectric breakdown, including all values and sub-ranges in between.Each spline (814) may include the insulated electrical leads of eachelectrode (816, 818) formed in a body of the spline (814) (e.g., withina lumen of the spline (814)). One or more spline wires (817, 819) may beelectrically conductive and electrically couple adjacent electrodes(816, 818) disposed on different splines (814). For example, the splinewires (817, 819) may extend in a transverse direction relative to alongitudinal axis of the ablation device (800).

FIG. 8B is a front cross-sectional view of FIG. 8A taken along the 8B-8Bline. Each spline wire (817, 819, 821, 823) electrically couples a pairof adjacent electrodes (816, 818, 820, 822) on different splines. Insome embodiments, each coupled electrode pair may be electricallyisolated from each other. In some embodiments, the coupled electrodepair may be configured with a common polarity. Adjacent pairs ofelectrodes may be configured with opposite polarities (e.g., a firstelectrode pair configured as an anode and an adjacent second electrodepair configured as a cathode). For example, the electrodes (816) coupledto a first set of spline wires (817) may be configured as an anode whileeach of the electrodes (818) coupled to a second set of spline wires(819) may be configured as a cathode. In some embodiments, eachelectrode formed on a spline (814) may share a common polarity (e.g.,configured as an anode or cathode). Each coupled electrode pair may beindependently addressable. In some embodiments, the ablation device(800) may include an even number of splines. The ablation device (800)may include any number of splines, for example, 4, 6, 8, 10, or moresplines. In some embodiments, the ablation device may include 4 to 10splines. For example, in one embodiment, the ablation device may include6 to 8 splines. As indicated in the foregoing, in some embodiments, thespline wires such as 817, 819, etc. can be replaced by similarelectrical connections in the proximal part of the device (for example,in the device handle). For example, the electrodes (816) can beelectrically wired together in the handle of the device, so that theseelectrodes are at the same electric potential during ablation.

FIG. 9A is a side view of yet another embodiment of an ablation device(900) including a catheter shaft (910) at a proximal end of the device(900), a distal cap (912) of the device (900), and a set of splines(914) coupled thereto. The distal cap (912) may include an atraumaticshape. A proximal end of the set of splines (914) may be coupled to adistal end of the catheter shaft (910), and a distal end of the set ofsplines (914) may be tethered to the distal cap (912) of the device(900). Each spline (914) of the ablation device (900) may include one ormore independently addressable electrodes (916, 918) formed on a surfaceof the spline (914). Each electrode (916, 918) may include an insulatedelectrical lead configured to sustain a voltage potential of at leastabout 700 V without dielectric breakdown of its correspondinginsulation. In other embodiments, the insulation on each of theelectrical leads may sustain an electrical potential difference ofbetween about 200V to about 2000 V across its thickness withoutdielectric breakdown. Each spline (914) may include the insulatedelectrical leads of each electrode (916, 918) formed in a body of thespline (914) (e.g., within a lumen of the spline (914)). FIG. 9Aillustrates a set of splines (914) where each spline (914) includes anelectrode spaced apart or offset from an electrode of an adjacent spline(914). For example, the set of splines (914) including a first spline(920) and a second spline (922) adjacent to the first spline (920),wherein an electrode (916) of the first spline (920) is disposed closerto a distal end (912) of the ablation device (900) relative to anelectrode (918) of the second spline (922). In other embodiments, thesize and shape of the electrodes (916, 918) may differ as well.

In some embodiments, adjacent distal electrodes (916) and proximalelectrodes (918) may form an anode-cathode pair. For example, the distalelectrodes (916) may be configured as an anode and the proximalelectrodes (918) may be configured as a cathode. In some embodiments,the ablation device (900) may include 3 to 12 splines. In FIG. 9A, oneelectrode (916, 918) is formed on a surface of each spline (914) suchthat each spline (914) includes one insulated electrical lead. A lumenof the spline (914) may therefore be reduced in diameter and allow thespline (914) to be thicker and more mechanically robust. Thus,dielectric breakdown of the insulation may be further reduced, therebyimproving reliability and longevity of each spline (914) and theablation device (900). The ablation device (900) may include any numberof splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, ormore splines. In some embodiments, the ablation device (900) may include3 to 20 splines. For example, in one embodiment, the ablation device(900) may include 6 to 10 splines. Furthermore, in some embodiments, theshape of a bulb-like expanded structure (930) of the expanded set ofsplines (914) may be asymmetric, for example with its distal portionbeing more bulbous or rounded than its proximal portion (e.g., see FIGS.9B-9E). Such a bulbous distal portion can aid in positioning the deviceat the ostium of a pulmonary vein.

Referring to FIGS. 9B-9E, it is understood that unless indicatedotherwise, components with similar references numbers to those in FIG.9A (e.g., the electrode (916) in FIG. 9A and the electrode (916′) inFIG. 9B) may be structurally and/or functionally similar. FIG. 9Billustrates the spline wires (914′, 920′, 922′) forming an expandedstructure (930′) during use such as when deployed. A first plane(924A′), also sometimes referred to as a proximal plane, of the expandedstructure (930′) has a cross-sectional area that is different than across-sectional area at a second plane (924B′) of the expanded structure(930′). As illustrated in FIG. 9B, in some embodiments, thecross-sectional area of the expanded structure (930′) at the secondplane (924B′) is greater than that at the first plane (924A′). The terms“first plane” and “second plane” as used with respect to FIG. 9B mayrefer to planes orthogonal to the longitudinal axis of the cathetershaft (910′) that are each formed up to about 1 cm, about 2 cm, andabout 3 cm or more (including all values and sub-ranges in between) fromthe distal end of the catheter shaft (910′) and the proximal end of thedistal cap (912′), respectively. Similar to FIG. 9A, the electrode(916′) of the first spline (920′) is disposed closer to the distal cap(912′) of the ablation device (900′) relative to an electrode (918′) ofthe second spline (922′).

FIG. 9C illustrates the spline wires (914″, 920″, 922″) forming anexpanded structure (930″) during use such as when deployed. A firstplane (924A″), also sometimes referred to as a proximal plane, of theexpanded structure (930″) has a cross-sectional area that is differentthan a cross-sectional area at a second plane (924B″) of the expandedstructure (930″). As illustrated in FIG. 9C, in some embodiments, thecross-sectional area of the expanded structure (930″) at the secondplane (924B″) is greater than that at the first plane (924A″). The terms“first plane” and “second plane” as used with respect to FIG. 9C mayrefer to planes orthogonal to the longitudinal axis of the cathetershaft (910″) that are each formed up to about 1 cm, about 2 cm, andabout 3 cm or more (including all values and sub-ranges in between) fromthe distal end of the catheter shaft (910″) and the proximal end of thedistal cap (912″), respectively. Unlike FIGS. 9A-9B, multiple electrodesmay be present on each spline wire, and some electrodes may beequidistant from the distal cap (912″). In this manner, relativelydistal electrodes such as 932″ and 934″ may be apposed at orproximal/antral to a pulmonary vein ostium during use for ablationdelivery to generate an ostial circumferential lesion around a pulmonaryvein.

FIG. 9D illustrates the spline wires (914″′, 920″′, 922′) forming anexpanded structure (930″′) during use such as when deployed. The splinewires (914′, 920′, 922″′) converge at their distal ends to a point(928″′) that lies inside/within the expanded structure (930′). Asillustrated in FIG. 9D, in such a configuration, at least someelectrodes (932″′, 934′) on the spline wires (914″′, 920″′, 922″′) maylie in a distal end plane (926″′) of the expanded structure (930″′). Theterm “distal end plane” as used with respect to FIG. 9D may refer to aplane orthogonal to the longitudinal axis of the catheter shaft (910″′)that passes through a distal boundary of the expanded structure (930′).In this manner, the expanded structure (930″′) may be pressed against,for example, an endocardial surface such as the posterior wall of theleft atrium in order to directly generate lesions thereupon byactivation of appropriate electrodes in the distal end plane using anysuitable combination of polarities. For example, distal electrodes(932″′, 934″′) may be pressed against an endocardial surface and used toform a lesion via focal ablation (e.g., a spot lesion).

Referring now to generation of focal ablation lesions using the ablationdevice (900″′), in some embodiments, the electrodes (933, 935) (alsosometimes referred to as “proximal electrodes”) and the electrodes(932′, 934″′) (also sometimes referred to as “distal electrodes”) may beactivated with opposite polarities. Conduction between these electrodesthrough the blood pool results in electric field generation andapplication of the electric field as ablative energy to the endocardialsurface present at the distal end plane (926″′), resulting in focalablation. For example, the spline wires (914″′, 920″′, 922′) may formthe expanded structure (930′) such that the distal electrodes (932″′,934″′) lie at or within the distal end plane (926′) of an endocardialsurface while the proximal electrodes (933, 935) lie outside the distalend plane (926″′) and consequently do not press against or otherwisecontact the endocardial surface. In some embodiments, the distalelectrodes (932′, 934′) may have the same polarity while adjacentproximal electrodes (935, 933) may have the opposite polarity to thedistal electrodes (932″′, 934″′).

In some embodiments, the electrodes of the ablation device (900″′) mayhave a length from about 0.5 mm to about 5.0 mm and a cross-sectionaldimension (e.g., a diameter) from about 0.5 mm to about 2.5 mm,including all values and subranges in between. The spline wires (914″′,920″′, 922″′) in the expanded structure (930″′) illustrated in FIG. 9Dmay have a cross-sectional dimension (e.g., a diameter) from about 6.0mm to about 30.0 mm, including all values and subranges in between. Thefocal ablation lesion formed in this manner may have a diameter betweenabout 0.5 cm to about 2.5 cm, including all values and subranges inbetween.

In some embodiments, the distal electrodes (932″′, 934″′) may beconfigured with opposite polarities. In some embodiments, adjacentelectrodes on the same spline may have the same polarity such thatdistal electrode (934″′) may have the same polarity as proximalelectrode (933) and likewise distal electrode (932″′) may have the samepolarity as proximal electrode (935). Electrodes (934″′, 933) may havethe opposite polarity as electrodes (932″′, 935).

In some embodiments, adjacent distal electrodes (934″′) and proximalelectrodes (933) may form an anode-cathode pair. For example, the distalelectrodes (934″′) may be configured as an anode and the proximalelectrodes (933) may be configured as a cathode. In another embodiment,the electrodes (2630) on one spline may alternate between an anode andcathode with the electrodes of an adjacent spline having a reverseconfiguration (e.g., cathode and anode).

FIG. 9E illustrates the spline wires (944, 940, 942) forming an expandedstructure (950) during use such as when deployed. The spline wires (944,940, 942) converge at their distal ends at a proximal end of a distalcap (912″″) inside/within the expanded structure (950). As illustratedin FIG. 9E, in such a configuration, at least some electrodes (952, 954)on the spline wires (944, 940) may lie in a distal end plane (946) ofthe expanded structure (950). The term “distal end plane” as used withrespect to FIG. 9E may refer to a plane orthogonal to the longitudinalaxis of the catheter shaft (910″″) that passes through a distal boundaryof the expanded structure (950). In this manner, the expanded structure(950) may be pressed against, for example, the posterior wall of theleft atrium in order to directly generate lesions thereupon byactivation of appropriate electrodes in the distal end plane (946) usingany suitable combination of polarities. For example, the electrodes 952and 954 may be configured with opposite polarities. Relative to theexpanded structure (930″″) in FIG. 9D, the expanded structure (950) inFIG. 9E has a more orthogonal (e.g., flattened) shape that may bepressed against, for example, the posterior wall of the left atrium fortissue ablation. In other words, the cross-sectional area of theexpanded structure (930″) at the distal end plane (926″) is less thanthat the cross-sectional area of the expanded structure (950) at thedistal end plane (946). As another example, distal electrodes (952, 954)may be pressed against an endocardial surface and used to form a lesionvia focal ablation (e.g., a spot lesion) as generally described hereinfor FIG. 9D.

For each of the ablation devices described herein, each of the splinesmay include a polymer and define a lumen so as to form a hollow tube.The one or more electrodes of the ablation device described herein mayinclude a diameter from about 0.2 mm to about 2.0 mm and a length fromabout 0.2 mm to about 5.0 mm. In some embodiments, the electrode mayinclude a diameter of about 1 mm and a length of about 1 mm. As theelectrodes may be independently addressable, the electrodes may beenergized in any sequence using any pulse waveform sufficient to ablatetissue by irreversible electroporation. For example, different sets ofelectrodes may deliver different sets of pulses (e.g., hierarchicalpulse waveforms), as discussed in further detail below. It should beappreciated that the size, shape, and spacing of the electrodes on andbetween the splines may be configured to deliver contiguous/transmuralenergy to electrically isolate one or more pulmonary veins. In someembodiments, alternate electrodes (for example, all the distalelectrodes) can be at the same electric potential, and likewise for allthe other electrodes (for example, all the proximal electrodes). Thusablation can be delivered rapidly with all electrodes activated at thesame time. A variety of such electrode pairing options exist and may beimplemented based on the convenience thereof.

FIG. 26A is a perspective view of an embodiment of an ablation device(2600) having a flower-like shape and including a catheter shaft (2610)at a proximal end of the device (2600), a distal cap (2612) of thedevice (2600), and a set of splines (2620) coupled thereto. As bestshown in FIG. 26B, a spline shaft (2614) may be coupled at a proximalend to the proximal handle (not shown) and coupled at a distal end tothe distal cap (2612). In preferred embodiments, the distance betweenthe distal cap (2612) and the catheter shaft (2610) may be less thanabout 8 mm. The spline shaft (2614) and distal cap (2612) may betranslatable along a longitudinal axis (2616) of the ablation device(2600). The spline shaft (2614) and distal cap (2612) may move together.The spline shaft (2614) may be configured to slide within a lumen of thecatheter shaft (2610). The distal cap (2612) may include an atraumaticshape to reduce trauma to tissue. A proximal end of each spline of theset of splines (2620) may pass through a distal end of the cathetershaft (2610) and be tethered to the catheter shaft within the cathetershaft lumen, and a distal end of each spline of the set of splines(2620) may be tethered to the distal cap (2612) of the device (2600).The ablation device (2600) may be configured for delivering a pulsewaveform, as disclosed for example in FIGS. 21-25, to tissue during usevia one or more splines of the set of splines (2620).

Each spline (2620) of the ablation device (2600) may include one or morejointly wired electrodes (2630) formed on a surface of the spline(2620), in some embodiments. In other embodiments, one or more of theelectrodes (2630) on a given spline may be independently addressableelectrodes (2630). Each electrode (2630) may include an insulatedelectrical lead configured to sustain a voltage potential of at leastabout 700 V without dielectric breakdown of its correspondinginsulation. In other embodiments, the insulation on each of theelectrical leads may sustain an electrical potential difference ofbetween about 200 V to about 2000 V across its thickness withoutdielectric breakdown. Each spline (2620) may include the insulatedelectrical leads of each electrode (2630) within a body of the spline(2620) (e.g., within a lumen of the spline (2620)). FIG. 26A illustratesa set of splines (2620) where each spline includes a set of electrodes(2632 or 2634) having about the same size, shape, and spacing as theelectrodes (2634 or 2632) of an adjacent spline (2620). In otherembodiments, the size, shape, and spacing of the electrodes (2632, 2634)may differ. The thickness of each spline (2620) may vary based on thenumber of electrodes (2630) formed on each spline (2620) which maycorrespond to the number of insulated electrical leads in the spline(2620). The splines (2620) may have the same or different materials,thickness, and/or length.

Each spline of the set of splines (2620) may include a flexiblecurvature so as to rotate, or twist and bend and form a petal-shapedcurve such as shown in FIGS. 26A-26C. The minimum radius of curvature ofa spline in the petal-shaped configuration may be in the range of about7 mm to about 25 mm. For example, the set of splines may form a deliveryassembly at a distal portion of the ablation device (2600) and beconfigured to transform between a first configuration where the set ofsplines are arranged generally parallel to the longitudinal axis of theablation device (2600), and a second configuration where the set ofsplines rotate around, or twist and bend, and generally bias away fromthe longitudinal axis of the ablation device (2600). In the firstconfiguration, each spline of the set of splines may lie in one planewith the longitudinal axis of the ablation device. In the secondconfiguration, each spline of the set of splines may bias away from thelongitudinal axis to form a petal-like curve arranged generallyperpendicular to the longitudinal axis. In this manner, the set ofsplines (2620) twist and bend and bias away from the longitudinal axisof the ablation device (2600), thus allowing the splines (2620) to moreeasily conform to the geometry of an endocardial space, and particularlyadjacent to the opening of a pulmonary ostium. The second configurationmay, for example, resemble the shape of a flower, when the ablationdevice is viewed from the front as best shown in FIG. 26C. In someembodiments, the each spline in the set of splines in the secondconfiguration may twist and bend to form a petal-like curve that, whenviewed from front, displays an angle between the proximal and distalends of the curve of more than 180 degrees. The set of splines mayfurther be configured to transform from a second configuration to athird configuration where the set of splines (2620) may be impressed(e.g., in contact with) against target tissue such as tissue surroundinga pulmonary vein ostium.

In some embodiments, the spline shaft (2614) coupled to the set ofsplines (2620) may allow each spline of the set of splines (2620) tobend and twist relative to the catheter shaft (2610) as the spline shaft(2614) slides within a lumen of the catheter shaft (2610). For example,the set of splines (2620) may form a shape generally parallel to alongitudinal axis of the spline shaft (2614) when undeployed, be wound(e.g., helically, twisted) about an axis (2660) parallel to thelongitudinal axis of the spline shaft (2620) when fully deployed, andform any intermediate shape (such as a cage or barrel) in-between as thespline shaft (2614) slides within a lumen of the catheter shaft (2610).

In some embodiments, the set of splines in the first configuration, suchas the spline (2620), may be wound about an axis (2660) parallel to thelongitudinal axis of the catheter shaft (2610) in some portions alongits length but elsewhere may otherwise be generally parallel to thelongitudinal axis of the catheter shaft (2610). The spline shaft (2614)may be retracted into the catheter shaft (2610) to transform theablation device (2600) from the first configuration to the secondconfiguration where the splines (2620) are generally angled or offset(e.g., perpendicular) with respect to the longitudinal axis of thecatheter shaft (2610) and twisted. As shown in the front view of FIG.26C, each spline (2620) may form a twisting loop in this front viewprojection. In FIG. 26C, each spline (2620) has a set of electrodes(2630) having the same polarity. As shown in the front view of FIG. 26C,each spline of the set of splines (2620) may form a twisted loop suchthat each spline overlaps one or more other splines. The number andspacing of the electrodes (2630), as well as the rotated twist of thespline (2620), may be configured by suitable placement of electrodesalong each spline to prevent overlap of an electrode (2630) on onespline with an electrode of an adjacent, overlapping spline (2620).

A spline having a set of anode electrodes (2632) may be activatedtogether to deliver pulse waveforms for irreversible electroporation.Electrodes on other splines may be activated together as cathodeelectrodes such as electrodes (2634) and (2635) on their respectivesplines so at to form an anode-cathode pairing for delivery of pulsewaveforms for irreversible electroporation, as shown in FIG. 26C. Theanode-cathode pairing and pulse waveform delivery can be repeatedsequentially over a set of such pairings.

For example, the splines (2620) may be activated sequentially in aclockwise or counter-clockwise manner. As another example, the cathodesplines may be activated sequentially along with respective sequentialanode spline activation until ablation is completed. In embodimentswhere electrodes on a given spline are wired separately, the order ofactivation within the electrode of each spline may be varied as well.For example, the electrodes in a spline may be activated all at once orin a predetermined sequence.

The delivery assembly may be disposed in the first configuration priorto delivering a pulse waveform and transformed to the secondconfiguration to make contact with the pulmonary vein ostium or antrum.In some of these embodiments, a handle may be coupled to the splineshaft (2614) and the handle configured for affecting transformation ofthe set of splines between the first configuration and the secondconfiguration. For example, the handle may be configured to translatethe spline shaft (2614) and distal cap (2612) relative to the cathetershaft (2610), thereby actuating the set of splines (2620) coupled to thedistal cap and causing them to bend and twist. The proximal ends of thesplines (2620) may be fixed to the spline shaft (2614) therebygenerating buckling of the splines (2620) resulting in a bending andtwisting motion of the splines (2620), for example, as the distal cap(2612) and spline shaft (2614) are pulled back relative to the cathetershaft (2610) that may be held by a user. For example, a distal end ofthe set of splines (2620) tethered to the distal cap (2612) may betranslated by up to about 60 mm along the longitudinal axis of theablation device to actuate this change in configuration. In other words,translation of an actuating member of the handle may bend and twist theset of splines (2620). In some embodiments, actuation of a knob, wheel,or other rotational control mechanism in the device handle may result ina translation of the actuating member or spline shaft and result inbending and twisting of the splines (2620). In some embodiments, theelectrical leads of at least two electrodes of the set of electrodes(2630) may be electrically coupled at or near a proximal portion of theablation device (2600), such as, for example, within the handle.

Retraction of the spline shaft (2614) and distal cap (2612) may bringthe set of splines (2620) closer together as shown in FIG. 26B where theset of splines (2620) are generally perpendicular to a longitudinal axisof the catheter shaft (2610). In some embodiments, each spline of theset of splines (2620) may be biased laterally away from the longitudinalaxis of the spline shaft (2614) by up to about 3 cm. In someembodiments, the spline shaft (2614) may include a hollow lumen. In someembodiments, the cross section of a spline may be asymmetric so as tohave a larger bending stiffness in one bending plane of the splineorthogonal to the plane of the cross section than in a different bendingplane. Such asymmetric cross sections may be configured to present arelatively larger lateral stiffness and thereby may deploy with minimaloverlap of the petal-shaped curves of each spline and its neighbors inthe final or fully-deployed configuration.

In one embodiment, each of the electrodes (2632) on a spline (2620) maybe configured as an anode while each of the electrodes (2634) on adifferent spline may be configured as a cathode. In another embodiment,the electrodes (2630) on one spline may alternate between an anode andcathode with the electrodes of another spline having a reverseconfiguration (e.g., cathode and anode).

In some embodiments, the spline electrodes may be electrically activatedin sequential manner to deliver a pulse waveform with each anode-cathodepairing. In some embodiments, the electrodes may be electrically wiredtogether within the spline, while in alternate embodiments they may bewired together in the handle of the device, so that these electrodes areat the same electric potential during ablation. In other embodiments,the size, shape, and spacing of the electrodes (2630) may differ aswell. In some embodiments, adjacent distal electrodes and proximalelectrodes may form an anode-cathode pair. For example, the distalelectrodes may be configured as an anode and the proximal electrodes maybe configured as a cathode.

The ablation device (2600) may include any number of splines, forexample, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or moresplines, including all values and sub-ranges in between. In someembodiments, the ablation device (2600) may include 3 to 20 splines. Forexample, the ablation device (2600) may include from 4 to 12 splines.

Each of the splines of the set of splines (2620) may include respectiveelectrodes (2630) having an atraumatic shape to reduce trauma to tissue.For example, the electrodes (2630) may have an atraumatic shapeincluding a rounded, flat, curved, and/or blunted portion configured tocontact endocardial tissue. In some embodiments, the electrodes (2630)may be located along any portion of the spline (2620) distal to thecatheter shaft (2610). The electrodes (2630) may have the same ordifferent sizes, shapes, and/or location along respective splines.

In this manner, the electrodes in the second configuration may be heldclose to or placed against a section of atrial wall of the left atriumin order to directly generate lesions thereupon by activation ofappropriate electrodes using any suitable combination of polarities, asdescribed herein. For example, the set of splines (2620) may be placedin contact against the atrial wall (2654) of atrium (2652) adjacent apulmonary vein (2650) (e.g., ostium or antrum).

FIG. 26D is a schematic illustration of ablation (2664) generated by theablation device (2600) on tissue, such as the tissue surrounding apulmonary vein ostium. For example, activation of one or more of theelectrodes (2630) on one or more of the splines (2620) may generate oneor more corresponding ablation areas (2664) along a wall (2654) of apulmonary vein antrum or ostium. In some embodiments, an outline of theablation areas (2664) in the pulmonary vein ostium may have a diameterof between about 2 cm and about 6 cm, and may be about 3.5 cm. In thismanner, a contiguous, transmural lesion may be generated, resulting inelectrical isolation of the pulmonary vein, which is a desiredtherapeutic outcome.

Alternatively, the ablation catheter with its deployed electrodes may beplaced adjacent to or against a section of posterior wall of the leftatrium, and by activation of suitable electrode sets, an appropriatepulse waveform may be delivered for irreversible electroporation energydelivery to ablate tissue.

In some embodiments, as the electrodes or a subset of electrodes may beindependently addressable, the electrodes may be energized in anysequence using any pulse waveform sufficient to ablate tissue byirreversible electroporation. For example, different sets of electrodesmay deliver different sets of pulses (e.g., hierarchical pulsewaveforms), as discussed in further detail herein. It should beappreciated that the size, shape, and spacing of the electrodes on andbetween the splines may be configured to deliver contiguous/transmuralenergy to electrically isolate one or more pulmonary veins. In someembodiments, alternate electrodes may be at the same electric potential,and likewise for all the other alternating electrodes. Thus, in someembodiments, ablation may be delivered rapidly with all electrodesactivated at the same time. A variety of such electrode pairing optionsexists and may be implemented based on the convenience thereof

FIGS. 27A-27B are side views of an embodiment of an ablation device(2700) including a catheter shaft (2710) at a proximal end of the device(2700) and a set of splines (2720) coupled to the catheter shaft (2710)at a distal end of the device (2700). The ablation device (2700) may beconfigured for delivering a pulse waveform to tissue during use via oneor more splines of the set of splines (2720). Each spline (2720) of theablation device (2700) may include one or more possibly independentlyaddressable electrodes (2730) formed on a surface (e.g., distal end) ofthe spline (2720). Each electrode (2730) may include an insulatedelectrical lead configured to sustain a voltage potential of at leastabout 700 V without dielectric breakdown of its correspondinginsulation. In other embodiments, the insulation on each of theelectrical leads may sustain an electrical potential difference ofbetween about 200V to about 2000 V across its thickness withoutdielectric breakdown. Each spline of the set of splines (2720) mayinclude the insulated electrical leads of each electrode (2730) formedin a body of the spline (2720) (e.g., within a lumen of the spline(2720)). In some embodiments, the electrodes (2730) may be formed at thedistal end of their respective spline (2720).

The set of splines (2720) may form a delivery assembly at a distalportion of the ablation device (2700) and be configured to transformbetween a first configuration and a second configuration. The set ofsplines (2720) in a first configuration are generally parallel to alongitudinal axis of the ablation device (2700) and may be closelyspaced together. The set of splines (2720) in a second configuration aredepicted in FIGS. 27A-27B where the set of splines (2720) extend out ofthe distal end of the catheter shaft (2710) and bias (e.g., curve) awayfrom the longitudinal axis of the ablation device (2700) and othersplines (2720). In this manner, the splines (2720) may more easilyconform to the geometry of an endocardial space. The delivery assemblymay be disposed in the first configuration prior to delivering a pulsewaveform and transformed to the second configuration to a section ofcardiac tissue such as the posterior wall of the left atrium, or aventricle. Such a device delivering irreversible electroporation pulsewaveforms may generate large lesions for focal ablations.

A distal end of the set of splines (2720) may be configured to bias awayfrom a longitudinal axis of the distal end of the catheter shaft (2710)and bias away from the other splines. Each spline of the set of splines(2720) may include a flexible curvature. The minimum radius of curvatureof a spline (2720) may be in the range of about 1 cm or larger.

In some embodiments, a proximal end of the set of splines (2720) may beslidably coupled to a distal end of the catheter shaft (2710).Accordingly, a length of the set of splines (2720) may be varied asshown in FIGS. 27A and 27B. As the set of splines (2720) are extendedfurther out from the catheter shaft (2710), the distal ends of the setof splines (2720) may bias further away from each other and alongitudinal axis of the catheter shaft (2710). The set of splines(2720) may be slidably advanced out of the catheter shaft (2710)independently or in one or more groups. For example, the set of splines(2720) may be disposed within the catheter shaft (2710) in the firstconfiguration. The splines (2720) may then be advanced out of thecatheter shaft (2710) and transformed into the second configuration. Thesplines (2720) may be advanced all together or advanced such that theset of splines (2720) corresponding to the anode electrodes (2730) areadvanced separately from the set of splines (2720) corresponding to thecathode electrodes (2730). In some embodiments, the splines (2720) maybe advanced independently. In the second configuration, the electrodes(2730) are biased away from the catheter shaft (2710) longitudinallyand/or laterally with respect to a longitudinal axis of a distal end ofthe catheter shaft (2710). This may aid delivery and positioning of theelectrodes (2730) against an endocardial surface. In some embodiments,each of the set of splines (2720) may extend from a distal end of thecatheter shaft (2710) by up to about 5 cm.

In some embodiments, the set of splines (2720) may have a fixed lengthfrom a distal end of the catheter shaft (2710). The splines (2720) mayextend from a distal end of the catheter shaft (2710) at equal orunequal lengths. For example, a spline having a greater radius ofcurvature than an adjacent spline may extend further from the cathetershaft (2710) than the adjacent spline. The set of splines (2720) may beconstrained by a lumen of a guide sheath, such that the set of splines(2720) are substantially parallel to the longitudinal axis of thecatheter shaft (2710) in the first configuration.

In some of these embodiments, a handle (not shown) may be coupled to theset of splines. The handle may be configured for affectingtransformation of the set of splines between the first configuration andthe second configuration. In some embodiments, the electrical leads ofat least two electrodes of the set of electrodes (2730) may beelectrically coupled at or near a proximal portion of the ablationdevice, such as, for example, within the handle. In this case theelectrodes (2730) may be electrically wired together in the handle ofthe device (2700), so that these electrodes (2730) are at the sameelectric potential during ablation.

Each of the splines of the set of splines (2720) may include respectiveelectrodes (2730) at a distal end of the set of splines (2720). The setof electrodes (2730) may include an atraumatic shape to reduce trauma totissue. For example, the electrodes (2730) may have an atraumatic shapeincluding a rounded, flat, curved, and/or blunted portion configured tocontact endocardial tissue. In some embodiments, the electrodes (2730)may be located along any portion of the spline (2720) distal to thecatheter shaft (2710). The electrodes (2730) may have the same ordifferent sizes, shapes, and/or location along respective splines.

In one embodiment, an electrode (2730) on a spline (2720) may beconfigured as an anode while an electrode (2730) on an adjacent spline(2720) may be configured as a cathode. The ablation device (2700) mayinclude any number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12,14, 16, 18, 20, or more splines, including all values and sub-ranges inbetween. In some embodiments, the ablation device (2700) may include 3to 20 splines. For example, the ablation device (2700) may include 6 to12 splines.

In FIGS. 27A-27B, one electrode (2730) is formed on a surface of eachspline (2720) such that each spline (2720) includes one insulatedelectrical lead. A lumen of the spline (2720) may therefore be reducedin diameter and allow the spline (2720) to be thicker and moremechanically robust. Thus, dielectric breakdown of the insulation may befurther reduced, thereby improving reliability and longevity of eachspline (2720) and the ablation device (2700). Furthermore, in someembodiments, the radius of curvature of the spline may vary over alength of the spline. For example, the radius of curvature may bemonotonically increasing. Such a variable radius of curvature may aid inpositioning the electrodes (2730) at some locations of endocardialtissue. The splines (2720) may have the same or different materials,thickness, and/or radius of curvature. For example, the thickness ofeach spline may reduce distally.

In this manner, the electrodes in the second configuration may bepressed against, for example, the posterior wall of the left atrium inorder to directly generate localized or focal lesions thereupon byactivation of appropriate electrodes using any suitable combination ofpolarities. For example, adjacent electrodes (2730) may be configuredwith opposite polarities.

As the electrodes or subsets of electrodes may be independentlyaddressable, the electrodes may be energized in any sequence using anypulse waveform sufficient to ablate tissue by irreversibleelectroporation. For example, different sets of electrodes may deliverdifferent sets of pulses (e.g., hierarchical pulse waveforms), asdiscussed in further detail herein. It should be appreciated that thesize, shape, and spacing of the electrodes on and between the splinesmay be configured to deliver transmural lesions over relatively wideareas of endocardial tissue. In some embodiments, alternate electrodesmay be at the same electric potential, and likewise for all the otheralternating electrodes. Thus, ablation may be delivered rapidly with allelectrodes activated at the same time. A variety of such electrodepairing options exists and may be implemented based on the conveniencethereof.

Referring to FIG. 27C, it is understood that unless indicated otherwise,components with similar references numbers to those in FIGS. 27A-27B(e.g., the electrode (2730) in FIGS. 27A-27B and the electrode (2730′)in FIG. 27C) may be structurally and/or functionally similar. FIG. 27Cillustrates a set of splines (2720′) where each spline (2720′) includesa pair of electrodes (2730′, 2740).

The ablation device (2700′) includes a catheter shaft (2710′) at aproximal end of the device (2700′) and a set of splines (2720′) coupledto the catheter shaft (2710′) at a distal end of the device (2700′). Theablation device (2700′) may be configured for delivering a pulsewaveform to tissue during use via one or more splines of the set ofsplines (2720′). Each spline (2720′) of the ablation device (2700′) mayinclude one or more independently addressable electrodes (2730′, 2740)formed on a surface of the spline (2720′). Each electrode (2730′, 2740)may include an insulated electrical lead configured to sustain a voltagepotential of at least about 700 V without dielectric breakdown of itscorresponding insulation. In other embodiments, the insulation on eachof the electrical leads may sustain an electrical potential differenceof between about 200V to about 2000 V across its thickness withoutdielectric breakdown. Each spline of the set of splines (2720′) mayinclude the insulated electrical leads of each electrode (2730′, 2740)formed in a body of the spline (2720′) (e.g., within a lumen of thespline (2720′)). Each electrode (2730′, 2740) of a spline (2720′) mayhave about the same size and shape. Furthermore, each electrode (2730′,2740) of a spline (2720′) may have about the same size, shape, andspacing as the electrodes (2730′, 2740) of an adjacent spline (2720′).In other embodiments, the size, shape, number, and spacing of theelectrodes (2730′, 2740) may differ.

In some embodiments, the electrodes (2730′, 2740) of the ablation device(2700′) may have a length from about 0.5 mm to about 5.0 mm and across-sectional dimension (e.g., a diameter) from about 0.5 mm to about4.0 mm, including all values and subranges in between. The spline wires(2720′) in the second configuration may splay out to an extent S_(d) ata distal end of the ablation device (2700′) from about 5.0 mm to about20.0 mm from each other (including all values and subranges in between),and may extend from a distal end of the catheter shaft (2710′) for alength S₁ from about 8.0 mm to about 20.0 mm, including all values andsubranges in between. In some embodiments, the ablation device (2700′)may include 4 splines, 5 splines, or 6 splines. In some embodiments,each spline may independently include 1 electrode, 2 electrodes, or 3 ormore electrodes.

The set of splines (2720′) may form a delivery assembly at a distalportion of the ablation device (2700′) and be configured to transformbetween a first configuration and a second configuration. The set ofsplines (2720′) in a first configuration are generally parallel to alongitudinal axis of the ablation device (2700) and may be closelyspaced together. The set of splines (2720′) in a second configurationare depicted in FIG. 27C where the set of splines (2720′) extend out ofthe distal end of the catheter shaft (2710′) and bias (e.g., curve) awayfrom the longitudinal axis of the ablation device (2700′) and othersplines (2720′). In this manner, the splines (2720′) may more easilyconform to the geometry of an endocardial space. The delivery assemblymay be disposed in the first configuration prior to delivering a pulsewaveform and transformed to the second configuration to contact a regionof endocardial tissue to generate large focal lesions upon delivery ofpulse waveforms for irreversible electroporation as disclosed herein. Insome embodiments, the electrodes (2730′) (also sometimes referred to as“distal electrodes”) in the second configuration depicted in FIG. 27Cmay be configured to contact and press against endocardial tissue whilethe electrodes (2740) (also sometimes referred to as “proximalelectrodes”) in the second configuration may not contact endocardialtissue. In this manner, an electric field generated by the electrodesdue to conduction between the proximal and distal electrodes through theblood pool results in focal ablation of tissue.

In some embodiments, a proximal end of the set of splines (2720′) may beslidably coupled to a distal end of the catheter shaft (2710′). As theset of splines (2720′) are extended further out from the catheter shaft(2710′), the distal ends of the set of splines (2720′) may bias furtheraway from each other and a longitudinal axis of the catheter shaft(2710′). The set of splines (2720′) may be slidably advanced out of thecatheter shaft (2710′) independently or in one or more groups. Forexample, the set of splines (2720′) may be disposed within the cathetershaft (2710′) in the first configuration. The splines (2720′) may thenbe advanced out of the catheter shaft (2710′) and transformed into thesecond configuration. The splines (2720′) may be advanced all togetheror advanced such that the set of splines (2720′) corresponding to theanode electrodes (2730) are advanced separately from the set of splines(2720′) corresponding to the cathode electrodes (2730′, 2740). In someembodiments, the splines (2710′) may be advanced independently throughrespective lumens (e.g., sheaths) of the catheter shaft (2710′). In thesecond configuration, the electrodes (2730′, 2740) are biased away fromthe catheter shaft (2710′) longitudinally and/or laterally with respectto a longitudinal axis of a distal end of the catheter shaft (2710′).This may aid delivery and positioning of the electrodes (2730′, 2740)against an endocardial surface. In some embodiments, each of the set ofsplines (2720′) may extend from a distal end of the catheter shaft(2710′) by up to about 5 cm.

In some embodiments, the distal electrodes (2730′) may have the samepolarity while adjacent proximal electrodes (2740) may have the oppositepolarity as the distal electrodes (2730′). In this manner, an electricfield may be generated between the distal and proximal electrodes forfocal ablation.

In some of these embodiments, a handle (not shown) may be coupled to theset of splines. The handle may be configured for affectingtransformation of the set of splines between the first configuration andthe second configuration. In some embodiments, the electrical leads ofat least two electrodes of the set of electrodes (2730′, 2740) may beelectrically coupled at or near a proximal portion of the ablationdevice, such as, for example, within the handle. In some embodiments,the electrodes (2730′, 2740) may be electrically wired together in thehandle of the device (2700′), so that these electrodes (2730′, 2740) areat the same electric potential during ablation.

The set of electrodes (2730′, 2740) may include an atraumatic shape toreduce trauma to tissue. For example, the electrodes (2730′, 2740) mayhave an atraumatic shape including a rounded, flat, curved, and/orblunted portion configured to contact endocardial tissue. In someembodiments, the electrodes (2730′, 2740) may be located along anyportion of the spline (2720′) distal to the catheter shaft (2710′). Theelectrodes (2730′, 2740) may have the same or different sizes, shapes,and/or location along respective splines. One or more of the splines(2720′) may include three or more electrodes.

In some embodiments, each of the electrodes (2730′) on a spline (2720′)may be configured as an anode while each of the electrodes (2730′) on anadjacent spline (2720′) may be configured as a cathode. In anotherembodiment, each of the electrodes (2730′) on one spline may alternatebetween an anode and cathode with each of the electrodes of an adjacentspline having a reverse configuration (e.g., cathode and anode). In someembodiments a subset of electrodes may be electrically wired together inthe handle of the device, so that these electrodes are at the sameelectric potential during ablation. In other embodiments, the size,shape, and spacing of the electrodes (2730) may differ as well. In someembodiments, adjacent distal electrodes (2730′) and proximal electrodes(2740) may form an anode-cathode pair. For example, the distalelectrodes (2730′) may be configured as an anode and the proximalelectrodes (2740) may be configured as a cathode.

The ablation device (2700′) may include any number of splines, forexample, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines,including all values and sub-ranges in between. In some embodiments, theablation device (2700′) may include 3 to 20 splines. For example, theablation device (2700) may include 6 to 12 splines.

In FIG. 27C, two electrodes (2730′, 2740) are formed on a surface ofeach spline (2720′) such that each spline (2720′) includes two insulatedelectrical leads. The thickness of each spline may vary based on thenumber of electrodes formed on each spline (2720′) which may correspondto the number of insulated electrical leads in the spline (2720′). Thesplines (2720′) may have the same or different materials, thickness,and/or radius of curvature. For example, the thickness of each spline(2720′) may reduce distally.

In this manner, the electrodes in the second configuration may be placedagainst, a section of endocardial tissue to directly generate lesionsthereupon by activation of appropriate electrodes using any suitablecombination of polarities for delivery of pulse waveforms forirreversible electroporation. For example, adjacent electrodes (2730′,2740) may be configured with opposite polarities.

As the electrodes may be independently addressable, the electrodes maybe energized in any sequence using any pulse waveform sufficient toablate tissue by irreversible electroporation. For example, differentsets of electrodes may deliver different sets of pulses (e.g.,hierarchical pulse waveforms), as discussed in further detail herein. Itshould be appreciated that the size, shape, and spacing of theelectrodes on and between the splines may be configured to delivercontiguous/transmural energy to electrically isolate one or morepulmonary veins. In some embodiments, alternate electrodes may be at thesame electric potential, and likewise for all the other alternatingelectrodes. Thus, ablation may be delivered rapidly with all electrodesactivated at the same time. A variety of such electrode pairing optionsexists and may be implemented based on the convenience thereof.

FIG. 28 is a side view of yet another embodiment of an ablation device(2800) including a catheter shaft (2810) at a proximal end of the device(2800), a distal cap (2812) of the device (2800), and a set of splines(2814) coupled thereto. In some embodiments, the ablation device (2800)is useful for forming lesions on endocardial surfaces via focalablation, as described herein.

The distal cap (2812) may include an atraumatic shape and one or moreindependently addressable electrodes (2816) (also sometimes referred toas “distal electrodes”), as described in further detail herein. Aproximal end of the set of splines (2814) may be coupled to a distal endof the catheter shaft (2810), and a distal end of the set of splines(2814) may be tethered to the distal cap (2812) of the device (2800).Each spline (2814) of the ablation device (2800) may include one or moreindependently addressable electrodes (2818) (also sometimes referred toas “proximal electrodes”) formed on a surface of the spline (2814). Eachelectrode (2816, 2818) may include an insulated electrical leadconfigured to sustain a voltage potential of at least about 700 Vwithout dielectric breakdown of its corresponding insulation. In otherembodiments, the insulation on each of the electrical leads may sustainan electrical potential difference of between about 200V to about 2000 Vacross its thickness without dielectric breakdown, including all valuesand subranges in between. Each spline (2814) may include the insulatedelectrical leads of each electrode (2818) formed in a body of the spline(2814) (e.g., within a lumen of the spline (2814)). One or more of thesplines (2818) may further include the insulated electrical lead of thedistal electrode (2816). In some embodiments, the size and/or shape ofthe electrodes (2816, 2818) may differ from each other.

The configuration of the set of splines (2814) and proximal electrodes(2818) may control a depth, shape, and/or diameter/size of a focalablation lesion generated by the ablation device (2800). The ablationdevice (2800) may be configured to transform between a firstconfiguration, where the set of splines (2814) are arranged generallyparallel to the longitudinal axis of the ablation device (2800), and asecond configuration, where the set of splines (2814) bow radiallyoutward from a longitudinal axis of the ablation device (2800). It isunderstood that the set of splines (2814) may be transformed into anyintermediate configuration between the first and second configurations,continuously or in discrete steps.

Activation of electrodes using a predetermined configuration may providetargeted and precise focal ablation by controlling a focal ablation spotsize based on the expansion of the splines (2814). For example, in someembodiments, a distal electrode (2816) may be configured with a firstpolarity and one or more proximal electrodes (2818) may be configuredwith a second polarity opposite the first polarity. When the proximalelectrodes (2818) of the ablation device (2800) are in the firstconfiguration, a high intensity electric field having a relativelysmaller/more focused diameter results in a focal ablation lesion on anendocardial surface that is relatively smaller in diameter and hasgreater depth. When the proximal electrodes (2818) of the ablationdevice (2800) are in the second configuration, a relatively moredispersed electric field is generated, resulting in a focal ablationlesion on an endocardial surface that is relatively wider and shallowerthan with the first configuration. In this manner, by varying the extentof expansion of the splines (2814), the depth, shape, and/or size of thelesion can be controlled without switching out the ablation device(2800). Such aspects are useful for creating multiple lesions of varyingsizes and/or depths using the same ablation device.

The distal cap (2812) may be disposed to press against the endocardialtissue while the proximal electrodes (2818) in either the first orsecond configurations may be configured so as to not contact endocardialtissue. It should be appreciated that the distal electrode (2816) neednot contact endocardial tissue. In some of these embodiments, a handle(not shown) may be coupled to the set of splines (2814) and the handleconfigured for affecting transformation of the set of splines (2814)between the first configuration and the second configuration. In someembodiments, the electrical leads of at least two electrodes of the setof electrodes may be electrically coupled at or near a proximal portionof the ablation device (2800), such as, for example, within the handle.

In some embodiments, the distal electrode (2816) and proximal electrodes(2818) may form anode-cathode pairs. For example, the distal electrode(2816) may be configured as an anode and each of the proximal electrodes(2818) may be configured as cathodes. In some embodiments, the ablationdevice (2800) may include 3 to 12 splines. The ablation device (2800)may include any number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10,12, 14, 16, 18, 20, or more splines. In some embodiments, the ablationdevice (2800) may include 3 to 20 splines. For example, in oneembodiment, the ablation device (2800) may include 6 to 10 splines.Furthermore, in some embodiments, the shape of the expanded set ofsplines (2814) may be asymmetric, for example with its distal portionbeing more bulbous or rounded than its proximal portion. Such a bulbousdistal portion (as well as proximal electrode positioning) may aid infurther controlling a size and depth of focal ablation.

A first plane (2822) depicted in FIG. 28 may refer to a plane orthogonalto the longitudinal axis of the catheter shaft (2810). The distal cap(2812) may be pressed against, for example, an endocardial surface lyingwithin the first plane (2812), such as a lumen wall of a pulmonary veinin order to directly generate focal ablation lesions thereupon byactivation of appropriate electrodes using any suitable combination ofpolarities. For example, distal electrode (2816) may be pressed againstan endocardial surface and used to form focal ablation lesions (e.g.,spot lesions). In some embodiments, one or more proximal electrodes(2818) may be configured with an opposite polarity to that of the distalelectrode (2816). Conversely, one or more of the proximal electrodes(2818) may be configured with the same polarity as the distal electrodes(2816). In some embodiments, the proximal electrodes (2818) on differentsplines (2814) may alternate between an anode and cathode.

In some embodiments, the distal electrode (2816) of the ablation device(2800) may include a length from about 0.5 mm to about 7.0 mm and across-sectional dimension (e.g., a diameter) from about 0.5 mm to about4.0 mm, including all values and subranges in between. In someembodiments, the proximal electrodes (2818) may include a length fromabout 0.5 mm to about 5.0 mm and a diameter from about 0.5 mm to about2.5 mm, including all values and subranges in between. The distalelectrode (2816) may be separated from the proximal electrodes (2818) bya length from about 3.0 mm to about 12.0 mm, including all values andsubranges in between. The distal electrode (2816) disposed on the distalcap (2812) may be located from about 1.0 mm to about 4.0 mm away from adistal end of the distal cap (2812) , including all values and subrangesin between. In some embodiments, the distal end of the distal cap (2812)may include the distal electrode (2816). One or more focal ablationzones may be formed including a diameter from about 1.0 cm to about 2.0cm, including all values and subranges in between.

FIGS. 29A-29D are side views of yet another embodiment of an ablationdevice (2900) including an outer catheter or sheath (2902) and a set ofinner catheters (2910, 2920) slidable within an outer catheter lumen soas to extend from a distal end of the lumen. The outer catheter maydefine a longitudinal axis. The inner diameter of the outer catheter(2902) may be about 0.7 mm to about 3 mm and the outer diameter of theouter catheter (2902) may be about 2 mm to about 5 mm. As best seen inFIGS. 29A, 29D, the ablation device (2900) includes a first catheter(2910) having a first proximal portion (2912), a first distal portion(2914), and a first electrode (2916) formed on the first distal portion(2914), such as on a surface of the first distal portion (2914), forexample. The first proximal portion (2912) may be coupled to the firstdistal portion (2914) via a first hinge (2918). A second catheter (2920)includes a second proximal portion (2922), a second distal portion(2924), and a second electrode (2926) formed on the second distalportion (2924). The second proximal portion (2922) may be coupled to thesecond distal portion (2924) via a second hinge (2928).

In some embodiments, the ablation device (2900) is useful for forminglesions on endocardial surfaces via focal ablation, as described herein.The distal ends of the catheters (2910, 2920) and/or the electrodes(2916, 2922) may include an atraumatic shape to reduce trauma to tissue.For example, the distal end of the catheters (2910, 2920) and/or theelectrodes (2916, 2922) may have an atraumatic shape including arounded, flat, curved, and/or blunted portion configured to contactendocardial tissue.

Each electrode (2916, 2926) may include an insulated electrical leadconfigured to sustain a voltage potential of at least about 700 Vwithout dielectric breakdown of its corresponding insulation. In otherembodiments, the insulation on each of the electrical leads may sustainan electrical potential difference of between about 200 V to about 2000V across its thickness without dielectric breakdown, including allvalues and subranges in between. Each catheter (2910, 2920) may includethe insulated electrical lead of each electrode (2916, 2926) formed in abody of the catheter (2910, 2920) (e.g., within a lumen of the catheter(2910, 2920)). Each of the electrodes (2916, 2926) may be connected to acorresponding insulated electrical lead leading to a handle (not shown)coupled to a proximal portion of the catheter (2910, 2920). In someembodiments, the size, shape, and/or location of the electrodes (2916,2926) may differ from each other.

In some embodiments, the configuration of the catheters (2910, 2920) andelectrodes (2916, 2926) may control a depth, shape, and/or diameter/sizeof a focal ablation lesion generated by the ablation device (2900). Thefirst and secfond catheters (2910, 2920) may be configured fortranslation along the longitudinal axis of the outer catheter (2902). Insome embodiments, the ablation device (2900) may be configured totransform between: a first configuration, where the set of catheters(2910, 2920) are arranged generally parallel to the longitudinal axis ofthe outer catheter (2902) and a distal portion of the catheters (2910,2920) are disposed within the outer catheter (2902) (e.g., FIG. 29A); asecond configuration, where the electrodes (2916, 2926) are advanced outof and away from the distal end (2903) of the outer catheter lumen(2902) by any suitable distance; and a third configuration, where adistal portion of each catheter (2910, 2920) may rotate, twist, or bendabout its corresponding hinge (2918, 2928) relative to a proximalportion of its corresponding catheter (2910, 2920) (e.g., FIGS.29B-29D). For example, as best illustrated in FIGS. 29B-29C, the firstcatheter (2910) may include a distal portion (2914) rotatable about afirst hinge (2918) that may be configured to position the distal portion(2914) relative to the proximal portion (2912) at a plurality ofpositions. The catheters (2910, 2912) in the second and thirdconfigurations may angle away from each other so as to bias away from alongitudinal axis of the outer catheter (2902). A distal end of theproximal portions (2912, 2922) may form an angle with respect to thelongitudinal axis between about 5 degrees and about 75 degrees (e.g.,FIG. 29D). It is understood that the ablation device (2900) may betransformed into any intermediate configuration between the first,second, and third configurations, continuously or in discrete steps.

In some embodiments, conduction between electrodes through the bloodpool and/or endocardial tissue results in electric field generation andapplication of the electric field as ablative energy to an endocardialsurface. The electrodes may be held close to or placed in physicalcontact against a section of atrial wall of the left atrium in order togenerate lesions thereupon by activation of one or more of theelectrodes using any suitable combination of polarities. In this manner,activation of electrodes using a predetermined configuration may providetargeted and precise focal ablation by controlling a focal ablation spotsize based on the position and orientation of the electrodes (2916,2926) relative to a proximal portion (2912, 2922) of the catheters(2910, 2920). For example, in some embodiments, a first electrode (2916)may be configured with a first polarity and a second electrode (2926)may be configured with a second polarity opposite the first polarity.When the electrodes (2916, 2926) are rotated such that they arerelatively close to each other (e.g., when the proximal portion (2912)and distal portion (2914) form an acute angle (2950)), a relativelyhigher intensity electric field that has a relatively smaller/morefocused diameter results in a focal ablation lesion on an endocardialsurface that is relatively smaller in diameter and has a good depth.Purely for non-limiting illustrative purposes, the acute angle formed atthe articulated hinge may range between about 15 degrees and about 70degrees. In some embodiments, the electric field intensity in the focalablation zone may be about 200 V/cm or more. When the electrodes (2916,2926) are rotated about their corresponding hinges (2918,2928) such thatthey are relatively farther from each other (e.g., when the proximalportion (2912) and distal portion (2914) form a larger angle), arelatively more dispersed and lower intensity electric field isgenerated, resulting in a focal ablation lesion on an endocardialsurface that is relatively wider and shallower. In this manner, byvarying the extent of rotation of the electrodes (2916, 2926) relativeto a proximal portion (2912, 2922) of the catheters (2910, 2920), thedepth, shape, and/or size of the lesion can be controlled withoutswitching out the ablation device (2900). Such aspects are useful forcreating multiple lesions of varying sizes, shapes, and/or depths usingthe same ablation device. For example, the lesion diameter may be fromabout 2 mm to about 3 cm, and the lesion depth may be between about 2 mmand about 12 mm. Although the electrodes (2916, 2926) may be disposed totouch endocardial tissue, it should be appreciated that the electrodes(2916, 2926) need not contact the endocardial tissue.

In some of these embodiments, a handle (not shown) may be coupled to theset of catheters (2910, 2920) and the handle configured for affectingtransformation of the catheters (2910, 2920) between the first, second,and third configurations. In some embodiments, actuation of one or moreknobs, wheels, sliders, pull wires, and/or other control mechanisms inthe handle may result in translation of one or more catheters (2910,2920) through the outer catheter (2902) and/or rotation of a distalportion (2914, 2924) of the catheter about a hinge (2918, 2928).

FIGS. 29B-29C depict a first catheter (2910) having an articulateddistal portion (2914). The first catheter (2910) may include a proximalportion (2912) coupled to a distal portion (2914) via a hinge (2918).The distal portion (2914) may include an electrode (2916) as describedherein. In some embodiments, the hinge (2918) may include a rotatablewheel. In other embodiments, the hinge (2918) may include a portion ofthe proximal portion (2912) or distal portion (2914) having a reducedcross-sectional area relative to the first catheter (2910) that is moreflexible than other portions of the catheter. In yet other embodiments,the hinge (2918) may include a joint, rotatable wheel, ball and socketjoint, condyloid joint, saddle joint, pivot, track, and the like.

The rotatable wheel may be coupled to a wire (2917) (e.g., pull wire).For example, the wire (2917) may be attached around the hinge (2918) andthe distal portion (2914) may be attached to a portion of the hinge(2918). Accordingly, actuation (2930) of the wire (2917) (e.g., pullingone end of the wire proximally) may in turn rotate the wheel (2918) andthe distal portion (2914) such that the distal portion (2914) rotatesrelative to the proximal portion (2912) of the first catheter (2910). Insome embodiments, the distal portion may rotate with respect to theproximal portion by an angle from about 110 degrees to about 165degrees, and the length of the distal portion may be from about 3 mm toabout 12 mm. A proximal end of the wire (2917) may in some embodimentsbe coupled to a handle (not shown) having a control mechanism (e.g., oneor more knobs, wheels, sliders). The operator may operate the controlmechanism to manipulate the wire (2917) to rotate the distal portion(2914) of the first catheter (2910) about the hinge (2918). The controlmechanism of the handle may include a lock to fix a position of thedistal portion (2914). FIG. 29B depicts an embodiment of the firstcatheter (2910) having the distal portion (2914) in between the secondand third configurations. FIG. 29C depicts an embodiment of the firstcatheter (2910) in the third configuration. The electrodes (2916, 2926)may bias towards each other in the third configuration.

FIG. 29D depicts an embodiment of the ablation device (2900) in thethird configuration, where distal portions of the first and secondcatheters (2910, 2920) are extended out of an outer catheter or sheath(2902) and rotated to a desired position (e.g., fully rotated, fullyarticulated) relative to proximal portions (2912, 2922) of the catheters(2910, 2920). In some embodiments, the wires (2912, 2922) of each of thecatheters (2910, 2920) may be coupled together at the handle such thatactuation of the control mechanism controls the wires (2912, 2922)together such that the distal portions (2914, 2924) of each of thecatheters (2910, 2920) may be simultaneously rotated about theirrespective hinges (2918, 2928). In the second and third configurations,the first and second catheters (2910, 2920) may bias away from thelongitudinal axis of the outer catheter (2902).

When the first and second catheters (2910, 2920) are extended out of theouter catheter (2902), one or more portions of the catheters (2910,2920) may assume their natural (e.g., unconstrained) shape(s), such as acurved shape. The catheters (2910, 2920) may be advanced out of theouter catheter (2902) together or independently. In some embodiments,the proximal portions (2912, 2922) of the catheters (2910, 2920) mayinclude a flexible curvature such that the distal ends of the catheters(2910, 2920) may be configured to splay away from each other. Theminimum radius of curvature of the catheter (2910, 2920) may be in therange of about 1 cm or larger. For example, the proximal portions (2912,2922) may have a radius of curvature of about 1 cm or larger. In someembodiments, the distal portions (2914, 2924) may have a radius ofcurvature of about 1 cm or larger.

In some embodiments, the electrodes (2916, 2926) of the ablation device(2900) may include a length from about 0.5 mm to about 7.0 mm and across-sectional dimension (e.g., a diameter) from about 0.5 mm to about4.0 mm, including all values and subranges in between. The electrodes(2916, 2926) of different catheters (2910, 2920) may be separated fromeach other by a distance from about 3.0 mm to about 20 mm, including allvalues and subranges in between. The electrode (2916, 2926) may belocated from about 1.0 mm to about 4.0 mm away from a distal end of itscorresponding catheter (2910, 2920), including all values and subrangesin between. In some embodiments, the distal end of the catheter (2910,2920) may include the electrode (2916, 2926). One or more focal ablationlesions may be formed including a diameter from about 1.0 cm to about2.0 cm, including all values and subranges in between.

FIG. 30 is a side view of another embodiment of an ablation device(3000) including an outer catheter or sheath (3010) defining alongitudinal axis and a set of four catheters (3020, 3030, 3040, 3050)slidable within a lumen (3010). Each of the catheters (3020, 3030, 3040,3050) may include a proximal portion (3023, 3033, 3043, 3053), distalportion (3024, 3034, 3044, 3054), and a hinge (3021, 3031, 3041, 3051)coupling the proximal portion (3023, 3033, 3043, 3053) to the distalportion (3024, 3034, 3044, 3054). Each of the distal portions (3024,3034, 3044, 3054) may include an electrode (3022, 3032, 3042, 3052). Thedistal ends of the catheters (3020, 3030, 3040, 3050) and/or theelectrodes (3022, 3032, 3042, 3052) may include an atraumatic shape(e.g., rounded, flat, curved, and/or blunted portion) to reduce traumato tissue. Each of the catheters (3020, 3030, 3040, 3050) may include ahinge (3021, 3031, 3041, 3051) as described in detail herein. It shouldbe appreciated that the ablation device (3000) may include any number ofcatheters including a set of 2, 3, 4, 5, 6, or more catheters.

Each electrode (3022, 3032, 3042, 3052) may include an insulatedelectrical lead configured to sustain a voltage potential of at leastabout 700 V without dielectric breakdown of its correspondinginsulation. In other embodiments, the insulation on each of theelectrical leads may sustain an electrical potential difference ofbetween about 200 V to about 2000 V across its thickness withoutdielectric breakdown, including all values and subranges in between.Each catheter (3020, 3030, 3040, 3050) may include the insulatedelectrical lead of each electrode (3022, 3032, 3042, 3052) formed in abody of the catheter (3020, 3030, 3040, 3050) (e.g., within a lumen ofthe catheter (3020, 3030, 3040, 3050)). Each of the electrodes (3022,3032, 3042, 3052) may be connected to a corresponding insulatedelectrical lead leading to a handle (not shown) coupled to a proximalportion of the catheter. In some embodiments, the size, shape, and/orlocation of the electrodes (3022, 3032, 3042, 3052) may differ from eachother.

In some embodiments, the configuration of the catheters (3020, 3030,3040, 3050) and electrodes (3022, 3032, 3042, 3052) may control a depth,shape, and/or diameter/size of a focal ablation lesion generated by theablation device (3000). The set of catheters (3020, 3030, 3040, 3050)may be configured to translate along the longitudinal axis to transitionbetween a first, second, and third configuration. In some embodiments,the ablation device (3000) may be configured to transform between: afirst configuration, where the set of catheters (3020, 3030, 3040, 3050)are arranged generally parallel to the longitudinal axis of the outercatheter or sheath (3010) and a distal portion of the catheters (3020,3030, 3040, 3050) are disposed within the outer catheter (3010); asecond configuration, where the electrodes (3022, 3032, 3042, 3052) areadvanced out of and away from a distal end (3011) of the outer catheter(3010) lumen by any suitable distance distance; and a thirdconfiguration, where a distal portion of each catheter (3020, 3030,3040, 3050) may rotate, twist, or bend about its corresponding hinge(3021, 3031, 3041, 3051) relative to a proximal portion of itscorresponding catheter (3020, 3030, 3040, 3050) (e.g., FIG. 30). Forexample, the first catheter (3020) may include a distal portion (3024)rotatable about a first hinge (3021) that may be configured to positionthe distal portion (3024) relative to the proximal portion (3023) at aplurality of positions as discussed above with respect to FIGS. 29A-29D.It is understood that the ablation device (3000) may be transformed intoany intermediate configuration between the first, second, and thirdconfigurations, continuously or in discrete steps. In the secondconfiguration, the set of catheters may bias away from the longitudinalaxis.

In some embodiments, one or more pulse waveforms may be applied betweenthe electrodes (3022, 3032, 3042, 3052) configured in anode and cathodesets. For example, adjacent or approximately diametrically opposedelectrode pairs may be activated together as an anode-cathode set. InFIG. 30, first electrode (3022) may be configured as an anode and pairedwith second electrode (3032) configured as a cathode. Third electrode(3042) may be configured as an anode and paired with fourth electrode(3052) configured as a cathode. The first and second electrode (3022,3032) pair may apply a first pulse waveform followed sequentially bysecond pulse waveform using the third and fourth electrode (3042, 3052)pair. In another embodiment, a pulse waveform may be appliedsimultaneously to each of the electrodes where the second and thirdelectrodes (3032, 3042) may be configured as anodes and the first andfourth electrodes (3022, 3052) may be configured as cathodes. It shouldbe appreciated that any of the pulse waveforms disclosed herein may beprogressively or sequentially applied over a sequence of anode-cathodeelectrodes. Some embodiments of the ablation device (3000) may have thesame dimensions as described above with respect to the ablation device(2900).

In other embodiments, one or more of the electrodes (3022, 3032, 3042,3052) may be configured with a first electrical polarity, while one ormore electrodes (not shown) disposed on a surface of the outer cathetershaft (3010) (not shown) may be configured with a second electricalpolarity opposite the first electrical polarity.

FIG. 31A-31B are perspective views of a yet another embodiment of anablation device (3100) including an outer catheter or sheath (3110)defining a longitudinal axis and a catheter (3160) slidable within aouter catheter lumen. The catheter (3160) may extend from a distal endof the lumen. The catheter (3160) may include a proximal portion (3160),multiple distal portions (3122, 3132, 3142, 3152), and articulation(3162) coupling the proximal portion to each of the multiple distalportions. For example, articulation (3162) may include a hinge, joint,rotatable wheel, ball and socket joint, condyloid joint, saddle joint,pivot, track, and the like. The distal portions (3122, 3132, 3142, 3152)are folded back within the outer catheter (3110) and internal springs(not shown) connecting to each portion are in a stressed configurationwhen each distal portion (3122, 3132, 3142, 3152) is folded. When thedistal portions (3122, 3132, 3142, 3152) are not constrained (i.e., whenthe inner catheter (3160) is deployed or pushed out far enough from theouter catheter (3110)), the springs assume their native or unstressedconfigurations resulting in articulation of the articulation (3162)whereupon the distal portions (3122, 3132, 3142, 3152) articulateoutward and assume a configuration approximately perpendicular to thelongitudinal axis of the catheter. As shown in FIG. 31B, the distal endof the catheter (3160) may be coupled to a set of electrodes (3120,3130, 3140, 3150) via articulation (3162). In some embodiments, thearticulation (3162) may be coupled to a first distal portion (3122), asecond distal portion (3132), a third distal portion (3142), and afourth distal portion (3152). The electrodes (3120, 3130, 3140, 3150)may be disposed on a surface of respective distal portions (3122, 3132,3142, 3152). When the catheter (3160) is advanced out of the outercatheter (3110), the distal portions (3120, 3130, 3140, 3150) may assumetheir natural (e.g., unconstrained) shapes so as to be approximatelyperpendicular to a longitudinal axis of the catheter (3160).

The electrodes (3120, 3130, 3140, 3150) may include an atraumatic shape(e.g., rounded, flat, curved, and/or blunted portion) to reduce traumato tissue. Each electrode (3120, 3130, 3140, 3150) may include aninsulated electrical lead configured to sustain a voltage potential ofat least about 700 V without dielectric breakdown of its correspondinginsulation. In other embodiments, the insulation on each of theelectrical leads may sustain an electrical potential difference ofbetween about 200 V to about 2000 V across its thickness withoutdielectric breakdown, including all values and subranges in between. Thecatheter (3160) may include the insulated electrical lead of eachelectrode (3120, 3130, 3140, 3150) formed in a body (e.g., lumen) of thecatheter (3160). Each of the electrodes (3120, 3130, 3140, 3150) may beconnected to a corresponding insulated electrical lead leading to ahandle (not shown) coupled to a proximal portion of the catheter (3160).In some embodiments, the size, shape, and/or location of the electrodes(3120, 3130, 3140, 3150) may differ from each other.

The catheter (3160) may be configured for translation along thelongitudinal axis to transition between a first, second, and thirdconfiguration. In some embodiments, the ablation device (3100) may beconfigured to transform between: a first configuration, where the set ofelectrodes (3120, 3130, 3140, 3150) are arranged generally parallel tothe longitudinal axis of the outer catheter (3110) and within the outercatheter (3110) (e.g., FIG. 31A); a second configuration, where the setof electrodes (3120, 3130, 3140, 3150) are advanced out of and away fromthe distal end (3111) of the outer catheter lumen by any suitabledistance (not shown in FIG. 31A); and a third configuration, where theelectrodes (3120, 3130, 3140, 3150) may rotate, twist, or bend about itscorresponding articulation (3162) relative to a proximal portion of thecatheter (3160) (e.g., FIG. 31B). The transition from the firstconfiguration to the second and third configurations may be performed byadvancing the catheter (3160) and electrodes (3120, 3130, 3140, 3150)out of a distal end of the outer catheter (3110). It is understood thatthe ablation device (3100) may be transformed into any intermediateconfiguration between the first, second, and third configurations,continuously or in discrete steps.

FIG. 31B illustrates the electrodes (3120, 3130, 3140, 3150) evenlyspaced apart to form a plus (“+”) shape. However, an angle betweenadjacent electrodes (3120, 3130, 3140, 3150) may be selected based upona desired focal ablation pattern. Similarly, the electrodes (3120, 3130,3140, 3150) in FIG. 31B are approximately perpendicular to thelongitudinal axis of the catheter (3160) but may be adjusted based upona set of ablation parameters.

In some embodiments, one or more pulse waveforms may be applied betweenthe electrodes (3120, 3130, 3140, 3150) configured in anode and cathodesets. For example, adjacent or approximately diametrically opposedelectrode pairs may be activated together as an anode-cathode set. InFIG. 31B, first electrode (3120) may be configured as an anode andpaired with third electrode (3140) configured as a cathode. Secondelectrode (3130) may be configured as an anode and paired with fourthelectrode (3150) configured as a cathode. The first and third electrode(3120, 3140) pair may apply a first pulse waveform followed sequentiallyby second pulse waveform using the second and fourth electrode (3130,3150) pair. In another embodiment, a pulse waveform may be appliedsimultaneously to each of the electrodes where the first and secondelectrodes (3120, 3130) may be configured as anodes and the third andfourth electrodes (3140, 3150) may be configured as cathodes. It shouldbe appreciated that any of the pulse waveforms disclosed herein may beprogressively or sequentially applied over a sequence of anode-cathodeelectrodes.

In other embodiments, one or more of the electrodes (3120, 3130, 3140,3150) may be configured with a first electrical polarity, and one ormore electrodes disposed on a surface of the outer catheter shaft (3110)may be configured with a second electrical polarity opposite the firstelectrical polarity.

FIG. 32 is a cross-sectional schematic view of a high intensity electricfield generated by an ablation device (3200) for ablation of tissue,such as tissue in a ventricular chamber. For example, the ablationdevice (3200) may be disposed in the endocardial space of the leftventricle of the heart. The ablation device (3200) depicted in FIG. 32may be similar to those ablation devices (3000, 3100) described withrespect to FIGS. 30 and 31A-31B. In some embodiments, the electrodes(3210, 3220, 3230, 3240) may be apposed to a tissue wall when in thethird configuration. In some embodiments, the electrodes (3210, 3220,3230, 3240) of FIG. 32 may have a width of between about 1 mm to about 3mm and a length of between about 3 mm and about 9 mm. For example, theelectrodes (3210, 3220, 3230, 3240) may have a width of about 2 mm and alength of about 6 mm.

In some embodiments, the electrodes (3210, 3220, 3230, 3240) may formanode-cathode pairs. For example, the first electrode (3210) may beconfigured as an anode and the third electrode (3230) may be configuredas a cathode. The first and second electrodes (3210, 3230) may have apotential difference of up to about 1500 V. Activation of one or more ofthe electrodes (3210, 3220, 3230, 3240) of one or more catheters maygenerate one or more ablation zones along a portion of the wall of acardiac chamber. Electric field contour (3350) is an iso-magnitude linecorresponding to an ablation zone (3350) having an electric fieldintensity threshold of about 460 V/cm when the first and thirdelectrodes (3220, 3240) are activated. In some embodiments, the ablationzone (3350) may have a width of up to about 12 mm and a length of up toabout 20 mm. Alternatively, the ablation device may be placed adjacentto or against a section of posterior wall of the left atrium, and byactivation of one or more electrodes, an appropriate pulse waveform maybe delivered for irreversible electroporation energy delivery to ablatetissue.

FIG. 33A is a perspective view of another embodiment of an ablationdevice/apparatus (3300) in the form of a catheter including an outershaft (3310) extending to a proximal end of the device (3300), an innershaft (3320) extending from a distal end of a shaft lumen (3312) of theouter shaft (3310), and a set of splines (3330) coupled thereto. Theinner shaft (3320) may be coupled at a proximal end to a handle (notshown) and disposed at a distal portion (e.g., a distal end) to a capelectrode (3322). The inner shaft (3320) and the set of splines (3330)may be translatable along a longitudinal axis (3324) of the ablationdevice (3300). In some embodiments, the inner shaft (3320) and the setof splines (3330) may move together or may be independently translated.The inner shaft (3320) may be configured to slide within the lumen(3312) of the outer shaft (3310). The cap electrode (3322) may includean atraumatic shape to reduce trauma to tissue. For example, the capelectrode (3322) may have a flat, circular shape and/or a rounded andblunt profile. A distal end of each spline of the set of splines (3330)may be tethered to a distal portion of the inner shaft (3320). Proximalportions of the set of splines (3330) may be attached to the outer shaft(3310). The ablation device (3300) may be configured for delivering apulse waveform, as disclosed for example in FIGS. 21-25, to tissueduring use via the electrodes (3332, 3334) on the splines (3330) and thedistal cap electrode (3322).

Each spline of the set of splines (3330) may include a set of electrodes(3332, 3334) on the surface of that spline. Each set of electrodes mayinclude a distal electrode (3332) such that the set of splines includesa set of distal electrodes (3332). Each of the distal electrodes (3332)are the nearest to the cap electrode (3322) relative to other electrodes(e.g., the set of proximal electrodes (3334)) of its corresponding setof electrodes on the same spline. Furthermore, in some embodiments, thedistal electrodes (3332) may have only an outward-facing exposedportion, i.e., a portion facing away from an inner space/volume definedby the set of splines. For example, if the distal electrodes (3332) areconstructed from metallic rings, a portion of each ring may be insulatedsuch that only an outward-facing exposed portion or “window” is exposedfor delivery of ablation energy. The cap electrode (3322) and eachdistal electrode (3332) of the set of distal electrodes may collectivelyhave the same polarity during use. This combination of closely-placeddistal electrodes having outward-facing windows and a cap electrodeallows the distal end of the ablation device (3300) to generate andproject a stronger electric field, and to thereby more effectivelygenerate focal ablation lesions of tissue at a desired depth compared toany one of these electrodes alone.

Each spline (3330) of the ablation device (3300) may include at least aset of independently addressable electrodes (3332, 3334) on the surfaceof that spline (3330). distal cap electrode (3322) may be formed at thedistal end of the catheter device (3300). Each electrode (3322, 3332,3334) may be coupled to an insulated electrical lead configured tosustain a voltage potential of at least about 700 V without dielectricbreakdown of its corresponding insulation. In other embodiments, theinsulation on each of the electrical leads may sustain an electricalpotential difference of between about 200 V to about 2000 V across itsthickness without dielectric breakdown. Each spline (3330) may includeinsulated electrical leads of each electrode (3332, 3334) within a bodyof the spline (3330) (e.g., within a lumen of the spline (3330)).Likewise, in some embodiments, the inner shaft (3320) may include aninsulated electrical lead for the cap electrode (3322). In otherembodiments, subsets of the electrodes (3322, 3332, 3334) may be jointlywired. For example, the proximal electrodes (3334) of each spline of theset of splines (3330) may be jointly wired. As another example, all thedistal electrodes (3332) and the cap electrode (3322) may be jointlywired.

In some embodiments, the set of splines (3330) may be configured totransform between a first configuration, where the set of splines (3330)are arranged generally parallel to the longitudinal axis (3324) of theablation device (3300), and a second configuration, where a distal endof each spline of the set of splines (3330) bows radially outward fromthe longitudinal axis (3324). In this manner, the set of distalelectrodes (3332) and the cap electrode (3322) may be shaped/oriented toform the second configuration shown in FIGS. 33A, 33B, and 33E. The capelectrode (3322) may be separated from each distal electrode of the setof distal electrodes (3332) by at most about 5 mm, including all valuesand sub-ranges in between. For example, the cap electrode (3322) may beseparated from each distal electrode of the set of distal electrodes(3332) by between about 0.5 mm and about 3 mm. In the secondconfiguration, the distal portion of each spline of the set of splines(3330) may be angled (3336) between about 45 degrees and about 90degrees relative to the longitudinal axis (3312), including all valuesand sub-ranges in between. For example, the distal portion of eachspline of the set of splines (3330) in the second configuration may beangled (3336) between about 70 degrees and about 80 degrees relative tothe longitudinal axis (3312). For example, in the second configuration,the cap electrode (3322) and set of distal electrodes (3332) can assumethe shape of a “plus” symbol when projected onto a plane perpendicularto the longitudinal axis (3324), as can be seen in the front view inFIG. 33B.

In some embodiments, the inner shaft (3320) may be retracted into theouter catheter lumen (3312) by a predetermined amount to transform theablation device (3300) from the first configuration to the secondconfiguration. It is understood that the set of splines (3330) may betransformed into any intermediate configuration between the first andsecond configurations, continuously or in discrete steps. The set ofsplines (3330) may form a shape generally parallel to a longitudinalaxis (3324) of the inner shaft (3320) when undeployed, and form abasket-like or bulb-like shape when a distal end of the set of splines(3330) bows radially outward from the longitudinal axis (3324).

FIGS. 33A, 33B, and 33E illustrate a set of splines (3330) where eachspline of the set of splines (3330) includes a distal electrode (3332)and one or more proximal electrodes (3334) that differ in one or more ofsize, shape, number, and spacing. For example, FIG. 33A illustrates onedistal electrode (3332) and two proximal electrodes (3334) for eachspline of the set of splines (3330). In some embodiments, each proximalelectrode (3334) may be formed on a surface of its spline (3330) alongits entire circumference, i.e., around the entire thickness of thespline. In some embodiments, each distal electrode (3332) may be formedon the surface of a portion of a circumference of its spline. That is,as shown in FIGS. 33C and 33D, the distal electrode (3332) may partiallylie on the circumference of its corresponding spline and not cover theentire circumference of its spline (3330). For example, the distalelectrode (3332) may encircle the circumference of its correspondingspline and be partially covered by a layer of insulation such that onlya portion (e.g., window) of the distal electrode (3332) is exposed. Insome embodiments, one or more electrodes may be fully covered by a thinlayer of insulation for biphasic operation. In some embodiments, the setof distal electrodes (3332) of the set of splines (3330) may subtend anangle (3333) of between about 30 degrees to about 300 degrees about acenter of its corresponding spline (3330), including all values andsub-ranges in between. For example, the set of distal electrodes (3332)of the set of splines (3330) may subtend an angle (3333) of betweenabout 60 degrees to about 120 degrees about a center of itscorresponding spline (3330). In this manner, a significant fraction ofthe electric field generated by the set of distal electrodes (3332) inthe second configuration may be directed in a forward direction andprojected into target tissue to aid focal ablation rather than away fromthe target tissue and into blood.

In this manner, the distal electrodes (3332) may be configured to face aparticular direction. For example, FIGS. 33A and 33E show the set ofdistal electrodes (3332) and the cap electrode (3322) facing generallyforward at the distal end of the device (3300) in the secondconfiguration when a distal end of the set of splines (3330) bowsradially outward from the longitudinal axis (3324). Furthermore, thedistal electrodes (3332) may be disposed at a distal end of its splinesuch that the distal electrodes (3332) of the set of splines (3330) aredisposed near to the cap electrode (3322).

In some embodiments, each spline of the set of splines (3330) mayinclude a set of electrodes (3332, 3334) having about the same size,shape, number, and spacing as the corresponding electrodes (3332, 3334)of an adjacent spline. The thickness of each spline (3330) may varybased on the number of electrodes (3332, 3334) formed on each spline(3330) which may correspond to the number of insulated electrical leadsin the spline (3330). The splines (3330) may have the same or differentmaterials, thickness, and/or length.

In some embodiments, the cap electrode (3322) and the set of electrodes(3332, 3334) may be configured in anode-cathode sets. For example, thecap electrode (3322) and each distal electrode of the set of distalelectrodes (3332) may be collectively configured as an anode, and allproximal electrodes (3334) may be collectively configured as a cathode(or vice-versa). In some embodiments, the set of distal electrodes(3332) and the set of proximal electrodes (3334) may have oppositepolarities. For example, the distal electrode (3332) and the set ofproximal electrodes (3334) for a given spline may have oppositepolarities. The cap electrode (3322) and the set of distal electrodes(3332) may have the same polarity. As discussed herein, the set ofdistal electrodes (3332) and the cap electrode (3322) may be jointlywired. In some embodiments, the cap electrode and the set of electrodes(3332, 3334) of one or more splines of the set of splines (3330) may beactivated together to deliver pulse waveforms for irreversibleelectroporation. In other embodiments, the pulse waveform delivery maybe repeated sequentially over predetermined subsets of the set ofelectrodes (3332, 3334).

In some embodiments, the set of distal electrodes (3332) may beseparated from the cap electrode (3322) by at most 3 mm from the distalend of each spline (3330). In some embodiments, the set of distalelectrodes (3332) may be separated from the set of proximal electrodes(3334) by between about 1 mm and about 20 mm. In some embodiments, eachelectrode of the set of electrodes (3332, 3334) may include a diameterof between about 0.5 mm to about 3 mm. In some embodiments, the capelectrode (3322) may include a cross-sectional diameter of between about1 mm and about 5 mm. In some embodiments, each electrode of the set ofelectrodes (3332, 3334) may have a length from about 0.5 mm to about 5mm. In some embodiments, the set of splines (3330) in the secondconfiguration may have an expanded cross-sectional diameter (i.e.,effective diameter of the expanded or second configuration at itslargest portion) of between about 6 mm and about 24 mm. In someembodiments, the set of splines (3300) may extend from the distal end(3312) of the outer shaft (3310) by between about 6 mm and about 30 mm.In some embodiments, the outer shaft (3310) may have an outer diameterof between about 1.5 mm and about 6.0 mm.

The ablation device (3300) as described herein may be disposed in thefirst configuration prior to delivering a pulse waveform and transformedto the second configuration to make contact with a tissue surface (e.g.,an inner wall of the left atrium or ventricle, and/or the like). In someof these embodiments, a handle (not shown) may be coupled to thecatheter (3300) and the set of splines (3330) and the handle configuredfor affecting transformation of the set of splines (3330) between thefirst configuration and the second configuration. For example, thehandle may be configured to translate the inner shaft (3320) relative tothe outer shaft (3310). For example, retracting the inner shaft (3320)into a lumen (3312) of the outer shaft (3310) may deploy the set ofsplines (3330) into the bulb-like shape illustrated herein. In someembodiments, actuation of a knob, wheel, or other control mechanism inthe device handle may result in translation of the inner shaft (3324)and result in deployment of the set of splines (3330). In someembodiments, the electrical leads of at least two electrodes of the setof electrodes (3322, 3332, 3334) may be electrically coupled at or neara proximal portion of the ablation device (3300), such as, for example,within the handle.

Furthermore, the catheter handle (not shown) may include a mechanism fordeflecting or steering the distal portion of the catheter device (3300).For example, a pull wire may extend from the catheter handle to one sideof the distal portion of the device (3300) at or near the distal end ofthe outer shaft (3310), with tensioning of the pull wire resulting indeflection of the distal portion of the device (3300). Deflection of thedevice (3300) may assist positioning of the device (3300) by a user at asuitable anatomical location in a controlled manner. In someembodiments, the distal cap electrode (3322) may be electrically wiredseparately from the distal spline electrodes (3332). In this manner,intracardiac ECG signals may be recorded only from the distal capelectrode (3322). In some embodiments, one or more distal splineelectrodes (3332) may be electrically wired separately, for monitoringof intracardiac ECG signals from each such electrode (3332). In someembodiments, some distal spline electrodes (3332) may be used for ECGmonitoring while other distal spline electrodes (3332) may be used fordelivery of ablation energy.

The ablation device (3300) may include any number of splines, forexample, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 20 or more splines,including all values and sub-ranges in between. In some embodiments, theablation device (3300) may include 3 to 20 splines. For example, theablation device (3300) may include from 4 to 12 splines.

Each of the splines of the set of splines (3300) may include respectiveelectrodes (3332, 3334) having an atraumatic, generally rounded shape toreduce trauma to tissue. In this manner, the distal electrodes in thesecond configuration may be held close to or placed against a section ofatrial wall of the left atrium in order to generate lesions thereupon byactivation of appropriate electrodes using any suitable combination ofpolarities, as described herein. For example, the cap electrode (3322)and the distal electrodes (3332) of the set of splines (3330) may beplaced in contact against or in close proximity to a tissue wall (3350),as shown in FIG. 33E, at either an approximately perpendicular or agenerally oblique orientation to a tissue wall. The configuration ofdistal electrodes (3322, 3332) allows the generation of a focal lesionat a desired depth even when the ablation device (3300) in the deployedconfiguration abuts the tissue wall (3350) at an angle (e.g.,obliquely).

In some embodiments, as the electrodes or a subset of electrodes may beindependently addressable, the electrodes may be energized in anysequence using any pulse waveform sufficient to ablate tissue byirreversible electroporation. For example, different sets of electrodesmay deliver different sets of pulses (e.g., hierarchical pulsewaveforms), as discussed in further detail herein. It should beappreciated that the size, shape, and spacing of the electrodes on andbetween the splines may be configured to deliver contiguous/transmuralenergy to electrically isolate one or more pulmonary veins. In someembodiments, alternate electrodes may be at the same electric potential,and likewise for all the other alternating electrodes. Thus, in someembodiments, ablation may be delivered rapidly with all electrodesactivated at the same time. A variety of such electrode pairing optionsexists and may be implemented based on the convenience thereof

In some embodiments, the ablation device (2900, 3000, 3100, 3200) mayinclude 2 to 6 catheters. The ablation device (2900, 3000, 3100, 3200)may include any number of catheters, for example, 2, 3, 4, 5, 6 or morecatheters. For example, in some embodiments, the ablation device (2900,3000, 3100, 3200) may include 3 to 6 catheters. In some embodiments, acatheter of an ablation device (2900, 3000, 3100, 3200) may include 2 to6 distal portions. The catheter may include any number of distalportions, for example, 2, 3, 4, 5, 6 or more distal portions. Forexample, in some embodiments, the catheter may include 2 to 4 distalportions. Furthermore, in some embodiments, the shape (e.g., curvature,length, size) of the catheters may be asymmetric to aid in controlling adepth, shape, and/or size of focal ablation.

In some embodiments, the electrodes may form anode-cathode pairs. Forexample, the first electrode may be configured as an anode and thesecond electrode may be configured as a cathode. In some embodiments, asubset of the electrodes may be independently addressable and theelectrodes may be energized in any sequence using any pulse waveformsufficient to ablate tissue by irreversible electroporation. Forexample, different sets of electrodes may deliver different sets ofpulses (e.g., hierarchical pulse waveforms).

In all the embodiments described in the foregoing and withoutlimitation, the ablation catheter itself may be a steerable device withpull wires for controlling deflection through a suitable mechanism inthe catheter handle, as is known to those skilled in the art.

Balloon

In some embodiments, an ablation device may include one or more balloonsfor delivering energy to ablate tissue by irreversible electroporation.FIG. 10 depicts an embodiment of a balloon ablation device (1010) (e.g.,structurally and/or functionally similar to the ablation device (110))disposed in a left atrial chamber (1000) of a heart. The ablation device(1010) may include a first balloon (1012) and a second balloon (1014)which may be configured to be disposed in an ostium (1002) of apulmonary vein (1004). The first balloon (1012) in an expanded (e.g.,inflated) configuration may have a larger diameter than the secondballoon (1014) in an expanded configuration. This allows the secondballoon (1014) to be advanced and disposed further into the pulmonaryvein (1014) while the first balloon (1012) may be disposed near and/orat an ostium (1002) of the pulmonary vein (1004). The inflated secondballoon serves to stabilize the positioning of the first balloon at theostium of the pulmonary vein. In some embodiments, the first balloon(1012) and the second balloon (1014) may be filled with any suitableconducting fluid such as, for example, saline. The first balloon (1012)and the second balloon (1014) may be electrically isolated from eachother. For example, each balloon (1012, 1014) may include an insulatedelectrical lead associated therewith, with each lead having sufficientelectrical insulation to sustain an electrical potential difference ofat least 700V across its thickness without dielectric breakdown. Inother embodiments, the insulation on each of the electrical leads maysustain an electrical potential difference of between about 200 V toabout 2500 V across its thickness without dielectric breakdown,including all values and sub-ranges in between. For example, a lead ofthe second balloon (1014) may be insulated as it extends through thefirst balloon (1012).

In some embodiments, the first and second balloons (1012, 1014) may forman anode-cathode pair. For example, in one embodiment, the first andsecond balloons may carry electrically separate bodies of saline fluid,and the first balloon (1012) may be configured as a cathode and thesecond balloon (1014) may be configured as an anode, or vice versa,where electrical energy may be capacitively coupled across the balloonor saline-filled electrodes. The device (1010) may receive a pulsewaveform to be delivered to tissue (1002). For example, one or more of abiphasic signal may be applied such that tissue may be ablated betweenthe first balloon (1012) and the second balloon (1014) at a desiredlocation in the pulmonary vein (1004). The first and second balloons(1012, 1014) may confine the electric field substantially between thefirst and second balloons (1012, 1014) so as to reduce the electricfield and damage to tissue away from the ostium (1002) of the pulmonaryvein (1004). In another embodiment, one or both of electrodes (1018) and(1019) disposed respectively proximal to and distal to the first balloonmay be used as an electrode of one polarity, while the fluid in thefirst balloon may act as an electrode of the opposite polarity. Abiphasic pulse waveform may then be delivered between these electrodesof opposed polarities by capacitive coupling across the balloon,resulting in a zone of irreversible electroporation ablation in theregion around the first balloon. In some embodiments, one or more of theballoons (1012, 1014) may include a wire mesh.

FIG. 11 is a cross-sectional view of another embodiment of a balloonablation device (1110) (e.g., structurally and/or functionally similarto the ablation device (1010)) disposed in a left atrial chamber (1100)and a right atrial chamber (1104) of a heart. The ablation device (1110)may include a balloon (1112) which may be configured to be advanced intoand disposed in the right atrial chamber (1104). For example, theballoon (1112) may be disposed in contact with a septum (1106) of theheart. The balloon (1112) may be filled with saline. The device (1110)may further include an electrode (1120) that may be advanced from theright atrial chamber (1104) through the balloon (1112) and the septum(1106) and into the left atrial chamber (1100). For example, theelectrode (1120) may extend from the balloon (1112) and puncture throughthe septum (1106) and be advanced into the left atrial chamber (1100).Once the electrode (1120) is advanced into the left atrial chamber(1100), a distal portion of the electrode (1120) may be modified to forma predetermined shape. For example, a distal portion of the electrode(1120) may include a nonlinear shape such as a circle, ellipsoid, or anyother geometric shape. In FIG. 11, the distal portion of the electrode(1120) forms a loop that may surround a single ostium or two or moreostia of the pulmonary veins (1102) in the left atrial chamber (1100).In other embodiments, the distal portion of the electrode (1120) mayhave about the same diameter as an ostium of the pulmonary vein (1102).

The balloon (1112) and the electrode (1120) may be electrically isolatedfrom each other. For example, the balloon (1112) and the electrode(1120) may each include an insulated electrical lead (1114, 1122)respectively, with each lead (1114, 1122) having sufficient electricalinsulation to sustain an electrical potential difference of at least700V across its thickness without dielectric breakdown. In otherembodiments, the insulation on each of the electrical leads may sustainan electrical potential difference of between about 200 V to about 2,000V across its thickness without dielectric breakdown, including allvalues and sub-ranges in between. The lead (1122) of the electrode(1120) may be insulated through the balloon (1112). In some embodiments,the saline in the balloon (1112) and the electrode (1120) may form ananode-cathode pair. For example, the balloon (1112) may be configured asa cathode and the electrode (1120) may be configured as an anode. Thedevice (1110) may receive a pulse waveform to be delivered to the ostiumof the pulmonary veins (1102). For example a biphasic signal may beapplied to ablate tissue. The pulse waveform may create an intenseelectric field around the electrode (1120) while the current is appliedvia capacitive coupling to the balloon (1112) to complete the circuit.In some embodiments, the electrode (1120) may include a fine gauge wireand the balloon (1112) may include a wire mesh.

In another embodiment, the electrode (1120) may be advanced through thepulmonary veins (1102) and disposed in one or more of the pulmonary veinostia without being advanced through the balloon (1112) and/or theseptum (1106). The balloon (1112) and electrode (1120) may be configuredas a cathode-anode pair and receive a pulse waveform in the same manneras discussed above.

Return Electrode

Some embodiments of an ablation system as described herein may furtherinclude a return electrode or a distributed set of return electrodescoupled to a patient to reduce the risk of unintended damage to healthytissue. FIGS. 12A-12B are schematic views of a set of return electrodes(1230) (e.g., return pad) of an ablation system disposed on a patient(1200). A set of four ostia of the pulmonary veins (1210) of the leftatrium are illustrated in FIGS. 12A-12B. An electrode (1220) of anablation device may be positioned around one or more of the ostia of thepulmonary veins (1210). In some embodiments, a set of return electrodes(1230) may be disposed on a back of a patient (1200) to allow current topass from the electrode (1220) through the patient (1200) and then tothe return electrode (1230).

For example, one or more return electrodes may be disposed on a skin ofa patient (1200). In one embodiment, eight return electrodes (1230) maybe positioned on the back of the patient so as to surround the pulmonaryvein ostia (1210). A conductive gel may be applied between the returnelectrodes (1230) and the skin to improve contact. It should beappreciated that any of the ablation devices described herein may beused with the one or more return electrodes (1230). In FIGS. 12A-12B,the electrode (1220) is disposed around four ostia (1210).

FIG. 12B illustrates the energized electrode (1220) forming an electricfield (1240) around the ostia (1210) of the pulmonary veins. The returnelectrode (1230) may in turn receive a pulsed monophasic and/or biphasicwaveform delivered by the electrode (1220). In some embodiments, thenumber of return electrodes (1230) may be approximately inverselyproportional to the surface area of the return electrodes (1230).

For each of the ablation devices discussed herein, the electrodes (e.g.,ablation electrode, return electrode) may include biocompatible metalssuch as titanium, palladium, silver, platinum or a platinum alloy. Forexample, the electrode may preferably include platinum or a platinumalloy. Each electrode may include an electrical lead having sufficientelectrical insulation to sustain an electrical potential difference ofat least 700V across its thickness without dielectric breakdown. Inother embodiments, the insulation on each of the electrical leads maysustain an electrical potential difference of between about 200V toabout 2500 V across its thickness without dielectric breakdown,including all values and sub-ranges in between. The insulated electricalleads may run to the proximal handle portion of the catheter from wherethey may be connected to a suitable electrical connector. The cathetershaft may be made of a flexible polymeric material such as Teflon,Nylon, Pebax, etc.

II. Methods

Also described here are methods for ablating tissue in a heart chamberusing the systems and devices described above. The heart chamber may bethe left atrial chamber and include its associated pulmonary veins.Generally, the methods described here include introducing and disposinga device in contact with one or more pulmonary vein ostial or antralregions. A pulse waveform may be delivered by one or more electrodes ofthe device to ablate tissue. In some embodiments, a cardiac pacingsignal may synchronize the delivered pulse waveforms with the cardiaccycle. Additionally or alternatively, the pulse waveforms may include aplurality of levels of a hierarchy to reduce total energy delivery. Thetissue ablation thus performed may be delivered in synchrony with pacedheartbeats and with less energy delivery to reduce damage to healthytissue. It should be appreciated that any of the ablation devicesdescribed herein may be used to ablate tissue using the methodsdiscussed below as appropriate.

In some embodiments, the ablation devices described herein may be usedfor focal ablation of cardiac features/structures identified to causearrhythmia. For example, a cardiac electrophysiology diagnostic catheter(e.g., mapping catheter) may be used to map cardiac structures such asrotors that may be subsequently ablated through focal ablation using anyof the ablation devices described herein. Focal ablation may, forexample, create a spot lesion that neutralizes a rotor while sparingsurrounding tissue. In some embodiments, one or more focal ablationlesions may be formed in combination with one or more box or linelesions to treat cardiac arrhythmia. As a non-limiting example, in someembodiments, a system can include one or more mapping catheters, one ormore ablation catheters (e.g., an ablation device as illustrated inFIGS. 9D, 9E, 27A-27C, 28, 29, 30, 31, 32) useful for creating lesionsvia focal ablation, and one or more catheters (e.g., an ablation deviceas illustrated in FIGS. 3-8, 9A-9C, 10-12, 26A-26B) useful for creatingbox and/or line lesions.

FIG. 13 is a method (1300) for one embodiment of a tissue ablationprocess. In some embodiments, the voltage pulse waveforms describedherein may be applied during a refractory period of the cardiac cycle soas to avoid disruption of the sinus rhythm of the heart. The method(1300) includes introduction of a device (e.g., ablation device, such asthe ablation device (110), and/or any of the ablation devices (200, 300,400, 500, 600, 700, 800, 900, 1010, 1110, 2900, 3000, 3100) into anendocardial space of a left atrium at step (1302). The device may beadvanced to be disposed in contact with a pulmonary vein ostium (1304).For example, electrodes of an ablation device may form an approximatelycircular arrangement of electrodes disposed in contact with an innerradial surface at a pulmonary vein ostium. In some embodiments, a pacingsignal may be generated for cardiac stimulation of the heart (1306). Thepacing signal may then be applied to the heart (1308). For example, theheart may be electrically paced with a cardiac stimulator to ensurepacing capture to establish periodicity and predictability of thecardiac cycle. One or more of atrial and ventricular pacing may beapplied. An indication of the pacing signal may be transmitted to asignal generator (1310). A time window within the refractory period ofthe cardiac cycle may then be defined within which one or more voltagepulse waveforms may be delivered. In some embodiments, a refractory timewindow may follow a pacing signal. For example, a common refractory timewindow may lie between both atrial and ventricular refractory timewindows.

A pulse waveform may be generated in synchronization with the pacingsignal (1312). For example, a voltage pulse waveform may be applied inthe common refractory time window. In some embodiments, the pulsewaveform may be generated with a time offset with respect to theindication of the pacing signal. For example, the start of a refractorytime window may be offset from the pacing signal by a time offset. Thevoltage pulse waveform(s) may be applied over a series of heartbeatsover corresponding common refractory time windows. The generated pulsewaveform may be delivered to tissue (1314). In some embodiments, thepulse waveform may be delivered to pulmonary vein ostium of a heart of apatient via one or more splines of a set of splines of an ablationdevice. In other embodiments, voltage pulse waveforms as describedherein may be selectively delivered to electrode subsets such asanode-cathode subsets for ablation and isolation of the pulmonary vein.For example, a first electrode of a group of electrodes may beconfigured as an anode and a second electrode of the group of electrodesmay be configured as a cathode. These steps may be repeated for adesired number of pulmonary vein ostial or antral regions to have beenablated (e.g., 1, 2, 3, or 4 ostia).

In some embodiments, hierarchical voltage pulse waveforms having anested structure and a hierarchy of time intervals as described hereinmay be useful for irreversible electroporation, providing control andselectivity in different tissue types. FIG. 14 is a flowchart (1400) ofanother embodiment of a tissue ablation process. The method (1400)includes the introduction of a device (e.g., ablation device, such asany of the ablation devices (200, 300, 400, 500, 600, 700, 800, 900,1010, 1110, 2900, 3000, 3100) into an endocardial space of a left atrium(1402). The device may be advanced to be disposed in a pulmonary veinostium (1404). In embodiments where the device may include a first andsecond configuration (e.g., compact and expanded), the device may beintroduced in the first configuration and transformed to a secondconfiguration to contact tissue at or near the pulmonary vein antrum orostium (1406). The device may include electrodes and may be configuredin anode-cathode subsets (1408) as discussed in detail above. Forexample, a subset of electrodes of the devices may be selected asanodes, while another subset of electrodes of the device may be selectedas cathodes, with the voltage pulse waveform applied between the anodesand cathodes.

A pulse waveform may be generated by a signal generator (e.g., thesignal generator 122) and may include a plurality of levels in ahierarchy (1410). A variety of hierarchical waveforms may be generatedwith a signal generator as disclosed herein. For example, the pulsewaveform may include a first level of a hierarchy of the pulse waveformincluding a first set of pulses. Each pulse has a pulse time durationand a first time interval separating successive pulses. A second levelof the hierarchy of the pulse waveform may include a plurality of firstsets of pulses as a second set of pulses. A second time interval mayseparate successive first sets of pulses. The second time interval maybe at least three times the duration of the first time interval. A thirdlevel of the hierarchy of the pulse waveform may include a plurality ofsecond sets of pulses as a third set of pulses. A third time intervalmay separate successive second sets of pulses. The third time intervalmay be at least thirty times the duration of the second level timeinterval.

It is understood that while the examples herein identify separatemonophasic and biphasic waveforms, it should be appreciated thatcombination waveforms, where some portions of the waveform hierarchy aremonophasic while other portions are biphasic, may also be generated. Avoltage pulse waveform having a hierarchical structure may be appliedacross different anode-cathode subsets (optionally with a time delay).As discussed above, one or more of the waveforms applied across theanode-cathode subsets may be applied during the refractory period of acardiac cycle. The pulse waveform may be delivered to tissue (1412). Itshould be appreciated that the steps described in FIGS. 13 and 14 may becombined and modified as appropriate.

FIGS. 15-18 depict embodiments of the methods for ablating tissue in aleft atrial chamber of the heart as described above using the ablationdevices described herein (e.g., FIGS. 2-5). FIG. 15 is a cross-sectionalview of an embodiment of a method to ablate tissue disposed in a leftatrial chamber of a heart using an ablation device (1500) correspondingto the ablation device (210) depicted in FIG. 2. The left atrial chamber(1502) is depicted having four pulmonary veins (1504) and the ablationdevice (1500) may be used to ablate tissue sequentially to electricallyisolate one or more of the pulmonary veins (1504). As shown in FIG. 15,the ablation device (1500) may be introduced into an endocardial spacesuch as the left atrial chamber (1502) using a trans-septal approach(e.g., extending from a right atrial chamber through the septum and intothe left atrial chamber (1502)). The ablation device (1500) may includea catheter (1510) and a guidewire (1520) slidable within a lumen of thecatheter (1510). A distal portion of the catheter (1510) may include aset of electrodes (1512). A distal portion (1522) of the guidewire(1520) may be advanced into the left atrial chamber (1502) so as to bedisposed near an ostium of a pulmonary vein (1504). The catheter (1510)may then be advanced over the guidewire (1520) to dispose the electrodes(1512) near the ostium of the pulmonary vein (1504). Once the electrodes(1512) are in contact with the ostium of the pulmonary vein (1504), theelectrodes (1512) may be configured in anode-cathode subsets. A voltagepulse waveform generated by a signal generator (not shown) may bedelivered to tissue using the electrodes (1512) in synchrony with pacedheartbeats and/or include a waveform hierarchy. After completion oftissue ablation in one of the pulmonary veins (1504), the catheter(1510) and guidewire (1520) may be repositioned at another pulmonaryvein (1504) to ablate tissue in one or more of the remaining pulmonaryveins (1504).

FIG. 16 is a cross-sectional view of an embodiment of a method to ablatetissue disposed in a left atrial chamber of a heart using an ablationdevice (1600) corresponding to the ablation device (310) depicted inFIG. 3. The left atrial chamber (1602) is depicted having four pulmonaryveins (1604) and the ablation device (1600) may be used to ablate tissuesequentially to electrically isolate one or more of the pulmonary veins(1604). As shown in FIG. 16, the ablation device (1600) may beintroduced into an endocardial space such as the left atrial chamber(1602) using a trans-septal approach. The ablation device (1600) mayinclude a sheath (1610) and a catheter (1620) slidable within a lumen ofthe sheath (1610). A distal portion (1622) of the catheter (1620) mayinclude a set of electrodes. A distal portion (1622) of the catheter(1620) may be advanced into the left atrial chamber (1602) to disposethe electrodes near an ostium of a pulmonary vein (1604). Once theelectrodes are in contact with the ostium of the pulmonary vein (1604),the electrodes may be configured in anode-cathode subsets. A voltagepulse waveform generated by a signal generator (not shown) may bedelivered to tissue using the electrodes in synchrony with pacedheartbeats and/or include a waveform hierarchy. After completion oftissue ablation in the pulmonary vein (1604), the catheter (1620) may berepositioned at another pulmonary vein (1604) to ablate tissue in one ormore of the remaining pulmonary veins (1604).

FIG. 17 is a cross-sectional view of an embodiment of a method to ablatetissue disposed in a left atrial chamber of a heart using an ablationdevice corresponding to the ablation device (410) depicted in FIG. 4.The left atrial chamber (1702) is depicted having four pulmonary veins(1704) and the ablation device (1700) may be used to ablate tissue toelectrically isolate one or more of the pulmonary veins (1704). As shownin FIG. 17, the ablation device (1700) may be introduced into anendocardial space such as the left atrial chamber (1702) using atrans-septal approach. The ablation device (1700) may include a sheath(1710) and a plurality of catheters (1720, 1721) slidable within a lumenof the sheath (1710). Each of the catheters (1720, 1721) may include arespective guidewire (1722, 1723) slidable within the catheter (1720,1721). A distal portion of the guidewire (1722, 1723) may include anelectrode configured to deliver a voltage pulse waveform. Each of thecatheters (1720, 1721) and corresponding guidewires (1722, 1723) may beadvanced into the left atrial chamber (1702) so as to be disposed nearrespective ostia of the pulmonary veins (1704). Once the guidewireelectrodes (1722, 1723) are in contact with the ostium of the pulmonaryvein (1704), the electrodes may be configured in anode-cathode subsets.For example, a first guidewire (1722) may be configured as an anodewhile a second guidewire (1723) may be configured as a cathode. In thisconfiguration, voltage pulse waveforms generated by a signal generator(not shown) may be delivered for ablation and simultaneous isolation ofthe pair of pulmonary veins (1704). Additionally or alternatively, avoltage pulse waveform may be delivered to tissue using the electrodesin synchrony with paced heartbeats and/or include a waveform hierarchy.After completion of tissue ablation in two of the pulmonary veins(1704), the catheters (1720, 1721) may be repositioned to ablate tissueat the two remaining pulmonary veins (1704). In some embodiments, thesheath (1710) may include three or four catheters to be disposed in thepulmonary veins (1704).

FIG. 18 is a cross-sectional view of an embodiment of a method to ablatetissue disposed in a left atrial chamber of a heart using an ablationdevice (1800) corresponding to the ablation device (500) depicted inFIG. 5. The left atrial chamber (1802) is depicted having four pulmonaryveins (1804) and the ablation device (1800) may be used to ablate tissuesequentially to electrically isolate one or more of the pulmonary veins(1804). As shown in FIG. 18, the ablation device may be introduced intoan endocardial space such as the left atrial chamber (1802) using atrans-septal approach. The ablation device may include a sheath (1820)and a catheter (1810) slidable within a lumen of the sheath (1820). Adistal portion (1812) of the catheter (1810) may be flower-shaped asdiscussed in detail with respect to FIG. 5. A distal portion (1812) ofthe catheter (1810) may be advanced into the left atrial chamber (1802)in a compact first configuration and disposed near an ostium of apulmonary vein (1804). The distal portion (1812) of the catheter (1810)may then be transformed to an expanded second configuration to form aflower-shaped distal portion, as shown in FIG. 18, such that the distalportion (1812) of the catheter (1810) is disposed near the ostium of thepulmonary vein (1804). Once the electrodes are in contact with theostium of the pulmonary vein (1804), the electrodes may be configured inanode-cathode subsets. A voltage pulse waveform generated by a signalgenerator (not shown) may be delivered to tissue using the electrodes insynchrony with paced heartbeats and/or include a waveform hierarchy.After completion of tissue ablation in the pulmonary vein (1804), thecatheter (1810) may be repositioned at another pulmonary vein (1804) toablate tissue in one or more of the remaining pulmonary veins (1804).

It should be appreciated that any of the methods described herein (e.g.,FIGS. 13-18) may further include coupling a return electrode (e.g., oneor more return electrodes (1230) depicted in FIGS. 12A-12B) to apatient's back and configured to safely remove current from the patientduring application of a voltage pulse waveform.

FIGS. 19A-20B depict embodiments of electrodes disposed in contactaround an ostium of a pulmonary vein and electric fields generatedtherefrom. FIG. 19A is a schematic representation (1900) of anembodiment of a set of electrodes (1910) disposed in an ostium of apulmonary vein (1904). A left atrial chamber (1902) may include a bloodpool (1906) and the pulmonary vein (1904) may include a blood pool(1908). The left atrial chamber (1902) and pulmonary vein (1904) mayeach have a wall thickness of up to about 4 mm.

FIG. 19B is another schematic representation (1900) of the set ofelectrodes (1910) disposed radially along an interior surface of apulmonary vein (1904). The pulmonary vein (1904) may include an arterialwall (1905) containing a blood pool (1908). Adjacent electrodes (1910)may be separated by a predetermined distance (1911). In someembodiments, the pulmonary vein (1904) may have an inner diameter ofabout 16 mm. In FIGS. 19A-19B, the electrodes (1910) may have a lengthof about 10 mm and be spaced apart about 4 mm from each other. It shouldbe appreciated that the electrodes (1910) may in other embodiments beany of the electrodes disclosed herein. For example, the electrodes(1910) may include the electrodes of the flower-shaped distal portion ofFIG. 5 and/or the generally circular arrangement of electrodes depictedin FIG. 3.

FIGS. 20A-20B are schematic representations (2000) of an embodiment ofan electric field (2020) generated by a set of electrodes (2010)disposed in an ostium of a pulmonary vein (2002). FIG. 20A is aperspective view while FIG. 20B is a cross-sectional view of thepulmonary vein (2002) and outer wall of the left atrial chamber (2004).The shaded electric field (2020) illustrates where the electric field(2020) exceeds a threshold value when adjacent electrodes (2010) deliverenergy (e.g., voltage pulse waveform) to ablate tissue. For example, theelectric field (2020) represents a potential difference of 1500 Vapplied between adjacent electrodes (2010). Under this applied voltage,the electric field (2020) magnitude is at least above a threshold valueof 500 V/cm within the shaded volumetric electric field (2020) and maybe sufficient to generate irreversible ablation in cardiac tissue. Bysequencing pulse waveforms over adjacent pairs of electrodes (2010) asdescribed above in detail, a pulmonary vein (2002) ostium may be ablatedto electrically isolate the pulmonary vein (2002) from the left atrialchamber (2004).

Pulse Waveform

Disclosed herein are methods, systems and apparatuses for the selectiveand rapid application of pulsed electric fields/waveforms to effecttissue ablation with irreversible electroporation. The pulse waveform(s)as disclosed herein are usable with any of the systems (100), devices(e.g., 200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 1230, 1500,1600, 1700, 1800, 1910, 2010, 2900, 3000, 3100), and methods (e.g.,1300, 1400) described herein. Some embodiments are directed to pulsedhigh voltage waveforms together with a sequenced delivery scheme fordelivering energy to tissue via sets of electrodes. In some embodiments,peak electric field values can be reduced and/or minimized while at thesame time sufficiently large electric field magnitudes can be maintainedin regions where tissue ablation is desired. This also reduces thelikelihood of excessive tissue damage or the generation of electricalarcing, and locally high temperature increases. In some embodiments, asystem useful for irreversible electroporation includes a signalgenerator and a processor capable of being configured to apply pulsedvoltage waveforms to a selected plurality or a subset of electrodes ofan ablation device. In some embodiments, the processor is configured tocontrol inputs whereby selected pairs of anode-cathode subsets ofelectrodes can be sequentially triggered based on a pre-determinedsequence, and in one embodiment the sequenced delivery can be triggeredfrom a cardiac stimulator and/or pacing device. In some embodiments, theablation pulse waveforms are applied in a refractory period of thecardiac cycle so as to avoid disruption of the sinus rhythm of theheart. One example method of enforcing this is to electrically pace theheart with a cardiac stimulator and ensure pacing capture to establishperiodicity and predictability of the cardiac cycle, and then to definea time window well within the refractory period of this periodic cyclewithin which the ablation waveform is delivered.

In some embodiments, the pulsed voltage waveforms disclosed herein arehierarchical in organization and have a nested structure. In someembodiments, the pulsed waveform includes hierarchical groupings ofpulses with a variety of associated timescales. Furthermore, theassociated timescales and pulse widths, and the numbers of pulses andhierarchical groupings, can be selected so as to satisfy one or more ofa set of Diophantine inequalities involving the frequency of cardiacpacing.

Pulsed waveforms for electroporation energy delivery as disclosed hereinmay enhance the safety, efficiency and effectiveness of the energydelivery by reducing the electric field threshold associated withirreversible electroporation, yielding more effective ablative lesionswith reduced total energy delivered. This in turn can broaden the areasof clinical application of electroporation including therapeutictreatment of a variety of cardiac arrhythmias.

FIG. 21 illustrates a pulsed voltage waveform in the form of a sequenceof rectangular double pulses, with each pulse, such as the pulse (2100)being associated with a pulse width or duration. The pulsewidth/duration can be about 0.5 microseconds, about 1 microsecond, about5 microseconds, about 10 microseconds, about 25 microseconds, about 50microseconds, about 100 microseconds, about 125 microseconds, about 140microseconds, about 150 microseconds, including all values andsub-ranges in between. The pulsed waveform of FIG. 21 illustrates a setof monophasic pulses where the polarities of all the pulses are the same(all positive in FIG. 21, as measured from a zero baseline). In someembodiments, such as for irreversible electroporation applications, theheight of each pulse (2100) or the voltage amplitude of the pulse (2100)can be in the range from about 400 volts, about 1,000 volts, about 5,000volts, about 10,000 volts, about 15,000 volts, including all values andsub ranges in between. As illustrated in FIG. 21, the pulse (2100) isseparated from a neighboring pulse by a time interval (2102), alsosometimes referred to as a first time interval. The first time intervalcan be about 10 microseconds, about 50 microseconds, about 100microseconds, about 200 microseconds, about 500 microseconds, about 800microseconds, about 1 millisecond including all values and sub ranges inbetween, in order to generate irreversible electroporation.

FIG. 22 introduces a pulse waveform with the structure of a hierarchy ofnested pulses. FIG. 22 shows a series of monophasic pulses such as pulse(2200) with pulse width/pulse time duration w, separated by a timeinterval (also sometimes referred to as a first time interval) such as(2202) of duration t₁ between successive pulses, a number mi of whichare arranged to form a group of pulses (2210) (also sometimes referredto as a first set of pulses). Furthermore, the waveform has a number m₂of such groups of pulses (also sometimes referred to as a second set ofpulses) separated by a time interval (2212) (also sometimes referred toas a second time interval) of duration t₂ between successive groups. Thecollection of m₂ such pulse groups, marked by (2220) in FIG. 22,constitutes the next level of the hierarchy, which can be referred to asa packet and/or as a third set of pulses. The pulse width and the timeinterval t₁ between pulses can both be in the range of microseconds tohundreds of microseconds, including all values and sub ranges inbetween. In some embodiments, the time interval t₂ can be at least threetimes larger than the time interval t₁. In some embodiments, the ratiot₂/t₁ can be in the range between about 3 and about 300, including allvalues and sub-ranges in between.

FIG. 23 further elaborates the structure of a nested pulse hierarchywaveform. In this figure, a series of mi pulses (individual pulses notshown) form a group of pulses (2300) (e.g., a first set of pulses). Aseries of m₂ such groups separated by an inter-group time interval(2310) of duration t₂ (e.g., a second time interval) between one groupand the next form a packet 132 (e.g., a second set of pulses). A seriesof m₃ such packets separated by time intervals (2312) of duration t₃(e.g., a third time interval) between one packet and the next form thenext level in the hierarchy, a super-packet labeled (2320) (e.g., athird set of pulses) in the figure. In some embodiments, the timeinterval t₃ can be at least about thirty times larger than the timeinterval t₂. In some embodiments, the time interval t₃ can be at leastfifty times larger than the time interval t₂. In some embodiments, theratio t₃/t₂ can be in the range between about 30 and about 800,including all values and sub-ranges in between. The amplitude of theindividual voltage pulses in the pulse hierarchy can be anywhere in therange from 500 volts to 7,000 volts or higher, including all values andsub ranges in between.

FIG. 24 provides an example of a biphasic waveform sequence with ahierarchical structure. In the example shown in the figure, biphasicpulses such as (2400) have a positive voltage portion as well as anegative voltage portion to complete one cycle of the pulse. There is atime delay (2402) (e.g., a first time interval) between adjacent cyclesof duration t₁, and n₁ such cycles form a group of pulses (2410) (e.g.,a first set of pulses). A series of n₂ such groups separated by aninter-group time interval (2412) (e.g., a second time interval) ofduration t₂ between one group and the next form a packet (2420) (e.g., asecond set of pulses). The figure also shows a second packet (2430),with a time delay (2432) (e.g., a third time interval) of duration t₃between the packets. Just as for monophasic pulses, higher levels of thehierarchical structure can be formed as well. The amplitude of eachpulse or the voltage amplitude of the biphasic pulse can be anywhere inthe range from 500 volts to 7,000 volts or higher, including all valuesand sub ranges in between. The pulse width/pulse time duration can be inthe range from nanoseconds or even sub-nanoseconds to tens ofmicroseconds, while the delays ti can be in the range from zero toseveral microseconds. The inter-group time interval t₂ can be at leastten times larger than the pulse width. In some embodiments, the timeinterval t₃ can be at least about twenty times larger than the timeinterval t₂. In some embodiments, the time interval t₃ can be at leastfifty times larger than the time interval t₂.

Embodiments disclosed herein include waveforms structured ashierarchical waveforms that include waveform elements/pulses at variouslevels of the hierarchy. The individual pulses such as (2200) in FIG. 22includes the first level of the hierarchy, and have an associated pulsetime duration and a first time interval between successive pulses. A setof pulses, or elements of the first level structure, form a second levelof the hierarchy such as the group of pulses/second set of pulses (2210)in FIG. 22. Among other parameters, associated with the waveform areparameters such as a total time duration of the second set of pulses(not shown), a total number of first level elements/first set of pulses,and second time intervals between successive first level elements thatdescribe the second level structure/second set of pulses. In someembodiments, the total time duration of the second set of pulses can bebetween about 20 microseconds and about 10 milliseconds, including allvalues and subranges in between. A set of groups, second set of pulses,or elements of the second level structure, form a third level of thehierarchy such as the packet of groups/third set of pulses (2220) inFIG. 22. Among other parameters, there is a total time duration of thethird set of pulses (not shown), a total number of second levelelements/second set of pulses, and third time intervals betweensuccessive second level elements that describe the third levelstructure/third set of pulses. In some embodiments, the total timeduration of the third set of pulses can be between about 60 microsecondsand about 200 milliseconds, including all values and sub ranges inbetween. The generally iterative or nested structure of the waveformscan continue to a higher plurality of levels, such as ten levels ofstructure, or more.

In some embodiments, hierarchical waveforms with a nested structure andhierarchy of time intervals as described herein are useful forirreversible electroporation ablation energy delivery, providing a gooddegree of control and selectivity for applications in different tissuetypes. A variety of hierarchical waveforms can be generated with asuitable pulse generator. It is understood that while the examplesherein identify separate monophasic and biphasic waveforms for clarity,it should be noted that combination waveforms, where some portions ofthe waveform hierarchy are monophasic while other portions are biphasic,can also be generated/implemented.

In some embodiments, the ablation pulse waveforms described herein areapplied during the refractory period of the cardiac cycle so as to avoiddisruption of the sinus rhythm of the heart. In some embodiments, amethod of treatment includes electrically pacing the heart with acardiac stimulator to ensure pacing capture to establish periodicity andpredictability of the cardiac cycle, and then defining a time windowwithin the refractory period of the cardiac cycle within which one ormore pulsed ablation waveforms can be delivered. FIG. 25 illustrates anexample where both atrial and ventricular pacing is applied (forinstance, with pacing leads or catheters situated in the right atriumand right ventricle respectively). With time represented on thehorizontal axis, FIG. 25 illustrates a series of ventricular pacingsignals such as (2500) and (2510), and a series of atrial pacing signals(2520, 2530), along with a series of ECG waveforms (2540, 2542) that aredriven by the pacing signals. As indicated in FIG. 25 by the thickarrows, there is an atrial refractory time window (2522) and aventricular refractory time window (2502) that respectively follow theatrial pacing signal (2522) and the ventricular pacing signal (2500). Asshown in FIG. 25, a common refractory time window (2550) of duration Trcan be defined that lies within both atrial and ventricular refractorytime windows (2522, 2502). In some embodiments, the electroporationablation waveform(s) can be applied in this common refractory timewindow (2550). The start of this refractory time window (2522) is offsetfrom the pacing signal (2500) by a time offset (2504) as indicated inFIG. 25. The time offset (2504) can be smaller than about 25milliseconds, in some embodiments. At the next heartbeat, a similarlydefined common refractory time window (2552) is the next time windowavailable for application of the ablation waveform(s). In this manner,the ablation waveform(s) may be applied over a series of heartbeats, ateach heartbeat remaining within the common refractory time window. Inone embodiment, each packet of pulses as defined above in the pulsewaveform hierarchy can be applied over a heartbeat, so that a series ofpackets is applied over a series of heartbeats, for a given electrodeset.

It should be understood that the examples and illustrations in thisdisclosure serve exemplary purposes and departures and variations suchas numbers of splines, number of electrodes, and so on can be built anddeployed according to the teachings herein without departing from thescope of this invention.

As used herein, the terms “about” and/or “approximately” when used inconjunction with numerical values and/or ranges generally refer to thosenumerical values and/or ranges near to a recited numerical value and/orrange. In some instances, the terms “about” and “approximately” may meanwithin ±10% of the recited value. For example, in some instances, “about100 [units]” may mean within ±10% of 100 (e.g., from 90 to 110). Theterms “about” and “approximately” may be used interchangeably.

Some embodiments described herein relate to a computer storage productwith a non-transitory computer-readable medium (also may be referred toas a non-transitory processor-readable medium) having instructions orcomputer code thereon for performing various computer-implementedoperations. The computer-readable medium (or processor-readable medium)is non-transitory in the sense that it does not include transitorypropagating signals per se (e.g., a propagating electromagnetic wavecarrying information on a transmission medium such as space or a cable).The media and computer code (also may be referred to as code oralgorithm) may be those designed and constructed for the specificpurpose or purposes. Examples of non-transitory computer-readable mediainclude, but are not limited to, magnetic storage media such as harddisks, floppy disks, and magnetic tape; optical storage media such asCompact Disc/Digital Video Discs (CD/DVDs), Compact Disc-Read OnlyMemories (CD-ROMs), and holographic devices; magneto-optical storagemedia such as optical disks; carrier wave signal processing modules; andhardware devices that are specially configured to store and executeprogram code, such as Application-Specific Integrated Circuits (ASICs),Programmable Logic Devices (PLDs), Read-Only Memory (ROM) andRandom-Access Memory (RAM) devices. Other embodiments described hereinrelate to a computer program product, which may include, for example,the instructions and/or computer code disclosed herein.

The systems, devices, and/or methods described herein may be performedby software (executed on hardware), hardware, or a combination thereof.Hardware modules may include, for example, a general-purpose processor(or microprocessor or microcontroller), a field programmable gate array(FPGA), and/or an application specific integrated circuit (ASIC).Software modules (executed on hardware) may be expressed in a variety ofsoftware languages (e.g., computer code), including C, C++, Java®, Ruby,Visual Basic®, and/or other object-oriented, procedural, or otherprogramming language and development tools. Examples of computer codeinclude, but are not limited to, micro-code or micro-instructions,machine instructions, such as produced by a compiler, code used toproduce a web service, and files containing higher-level instructionsthat are executed by a computer using an interpreter. Additionalexamples of computer code include, but are not limited to, controlsignals, encrypted code, and compressed code.

The specific examples and descriptions herein are exemplary in natureand embodiments may be developed by those skilled in the art based onthe material taught herein without departing from the scope of thepresent invention, which is limited only by the attached claims.

1.-86. (canceled)
 87. An apparatus, comprising: a catheter defining alongitudinal axis; a distal portion; a plurality of electrodes; a set ofsplines, each spline of the set of splines including: a set ofelectrodes from the plurality of electrodes formed on that spline, eachset of electrodes including (1) a distal electrode such that the set ofsplines includes a set of distal electrodes and (2) a proximal electrodesuch that the set of splines includes a set of proximal electrodes; aproximal end coupled to a distal end of the catheter, the distal endcoupled to the distal portion; the set of splines configured fortranslation along the longitudinal axis to transition between: a firstconfiguration in which the set of splines are approximately parallel tothe longitudinal axis; and a second configuration in which a distalportion of each spline of the set of splines is bowed radially outwardfrom the longitudinal axis.
 88. The apparatus of claim 87, wherein thedistal electrode and the proximal electrode formed on each spline fromthe set of splines are configured to be activated with oppositeelectrical polarities to generate energy for ablating tissue.
 89. Theapparatus of claim 88, wherein the set of distal electrodes arecollectively configured as an anode and the set of proximal electrodesare collectively configured as a cathode, to act as an anode-cathodepair for generating the energy for ablating tissue.
 90. The apparatus ofclaim 87, wherein, when the set of splines are in the secondconfiguration, at least one electrode from the set of distal electrodesis configured to contact a tissue surface and form a focal ablationlesion on the tissue surface having a diameter between about 0.5 cm andabout 2.5 cm.
 91. The apparatus of claim 87, wherein the set of splineswhen in the second configuration forms an expanded structure having adiameter from about 6.0 mm to about 30.0 mm.
 92. The apparatus of claim87, wherein the set of splines when in the second configuration forms anexpanded structure having an asymmetrical shape in which a distalportion of the expanded structure has an outer diameter larger than thatof a proximal portion of the expanded structure.
 93. The apparatus ofclaim 87, wherein each distal electrode from the set of distalelectrodes is at the same distance from the distal portion of theapparatus.
 94. The apparatus of claim 87, wherein each spline from theset of splines includes a set of insulated electrical leads disposedtherein, each insulated electrical lead from the set of insulatedelectrical leads electrically coupled to at least one spline from theset of splines formed on that spline and configured to sustain a voltagepotential of at least about 700 V without dielectric breakdown of itscorresponding insulation.
 95. The apparatus of claim 87, wherein eachelectrode from the set of electrodes has a length between about 0.5 mmand about 5 mm.
 96. The apparatus of claim 87, wherein each spline fromthe set of splines includes a plurality of proximal electrodes and atleast one flexible portion is disposed between the plurality ofelectrodes for increasing flexibility of the set of splines at alocation of the plurality of proximal electrodes.
 97. An apparatus,comprising: a catheter defining a longitudinal axis; a distal portion; aplurality of electrodes; a set of splines, each spline of the set ofsplines including: a set of electrodes from the plurality of electrodesformed on that spline, each set of electrodes including (1) a distalelectrode such that the set of splines includes a set of distalelectrodes and (2) a proximal electrode such that the set of splinesincludes a set of proximal electrodes; a proximal end coupled to adistal end of the catheter, the distal end coupled to the distalportion; the set of splines configured to transition between a firstconfiguration and a second configuration in which the set of distalelectrodes is disposed in a distal end plane that is generallyperpendicular with respect to the longitudinal axis and the set ofproximal electrodes is disposed outside the distal end plane.
 98. Theapparatus of claim 97, wherein the set of splines when in the secondconfiguration forms an expanded structure having an asymmetrical shapein which a distal portion of the expanded structure has an outerdiameter larger than that of a proximal portion of the expandedstructure.
 99. The apparatus of claim 97, wherein, when the set ofsplines are in the second configuration, at least one electrode from theset of distal electrodes is configured to contact a tissue surfacedisposed in the distal end plane and apply ablative energy to the tissuesurface.
 100. The apparatus of claim 99, wherein the distal electrodeand the proximal electrode formed on each spline from the set of splinesare configured to be activated with opposite electrical polarities togenerate the ablative energy.
 101. The apparatus of claim 100, whereinthe set of distal electrodes are collectively configured as an anode andthe set of proximal electrodes are collectively configured as a cathode,to act as an anode-cathode pair for generating the ablative energy. 102.The apparatus of claim 99, wherein the plurality of electrodes areconfigured to form a lesion on the tissue surface having a diameterbetween about 0.5 cm and about 2.5 cm.
 103. An apparatus, comprising: acatheter defining a longitudinal axis; a distal portion; a plurality ofelectrodes; a set of splines, each spline of the set of splinesincluding: a set of electrodes from the plurality of electrodes formedon that spline, each set of electrodes including (1) a distal electrodesuch that the set of splines includes a set of distal electrodes and (2)a proximal electrode such that the set of splines includes a set ofproximal electrodes; a proximal end coupled to a distal end of thecatheter, the distal end coupled to the distal portion; each distalelectrode from the distal set of electrodes configured to have the sameelectrical polarity during use.
 104. The apparatus of claim 103, whereineach spline from the set of splines includes a plurality of proximalelectrodes and at least one flexible portion is disposed between theplurality of electrodes for increasing flexibility of the set of splinesat a location of the plurality of proximal electrodes.
 105. Theapparatus of claim 103, wherein each distal electrode from the set ofdistal electrodes is at the same distance from the distal portion of theapparatus.
 106. The apparatus of claim 103, wherein the set of splinesare configured for translation along the longitudinal axis to transitionbetween: a first configuration in which the set of splines areapproximately parallel to the longitudinal axis; and a secondconfiguration in which a distal portion of each spline of the set ofsplines is bowed radially outward from the longitudinal axis.
 107. Amethod of focal ablation via irreversible electroporation, comprising:delivering an ablation device to a cardiac chamber of a heart of apatient, the ablation device defining a longitudinal axis and comprisinga set of splines, each spline from the set of splines including a set ofelectrodes formed on a surface of that spline, each set of electrodesincluding (1) a distal electrode such that the set of splines includes aset of distal electrodes and (2) a proximal electrode such that the setof splines includes a set of proximal electrodes; transitioning the setof splines between a first configuration and a second configuration inwhich the set of distal electrodes is disposed in a distal end planethat is generally perpendicular with respect to the longitudinal axisand the set of proximal electrodes is disposed outside the distal endplane; generating a pulse waveform; and delivering the pulse waveform toa portion of a wall of the cardiac chamber via at least one spline ofthe set of splines.
 108. The method of claim 107, wherein the set ofsplines when in the second configuration forms an expanded structurehaving an asymmetrical shape in which a distal portion of the expandedstructure has an outer diameter larger than that of a proximal portionof the expanded structure.
 109. The method of claim 107, furthercomprising contacting a tissue surface disposed in the distal end planewhen the set of splines are in the second configuration and applyingablative energy to the tissue surface.
 110. The method of claim 109,wherein the distal electrode and the proximal electrode formed on eachspline from the set of splines are configured to be activated withopposite electrical polarities to generate the ablative energy.
 111. Themethod of claim 110, wherein the set of distal electrodes arecollectively configured as an anode and the set of proximal electrodesare collectively configured as a cathode, to act as an anode-cathodepair for generating the ablative energy.
 112. The method of claim 109,wherein the set of splines are configured to form a lesion on the tissuesurface having a diameter between about 0.5 cm and about 2.5 cm. 113.The method of claim 109, wherein the tissue surface is a pulmonary veinostium.
 114. The method of claim 107, wherein the cardiac chamber is anendocardial space of an atrium.
 115. The method of claim 107, whereineach electrode of the set of electrodes has an insulated electrical leadassociated therewith, each insulated electrical lead configured forsustaining a voltage potential of at least about 700 V withoutdielectric breakdown of its corresponding insulation.
 116. The method ofclaim 107, wherein each spline from the set of splines includes aplurality of proximal electrodes and at least one flexible portiondisposed between the plurality of electrodes for increasing flexibilityof the set of splines at a location of the plurality of proximalelectrodes.